Analysis of the rs20541 (R130Q) Polymorphism in the IL-13 Gene in Patients With Elderly-associated Chronic Inflammatory Diseases

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Los datos se representan de forma conjunta para los pacientes con enfermedad activa de las tres patologías incluidas en el estudio (N.° total=114: arteritis de células gigantes [ACG; N = 15], polimialgia reumática [PMR; N =71] y artritis reumatoide de inicio en el anciano [EORA; N = 28])." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lorena Álvarez-Rodríguez, Marcos López-Hoyos, Eugenio Carrasco-Marín, Cristina Mata, Jaime Calvo-Alén, Elena Aurrecoechea, Ricardo Blanco, Teresa Ruiz, Pedro Muñoz Cacho, Ignacio Villa, Víctor Manuel Martínez-Taboada" "autores" => array:11 [ 0 => array:2 [ "nombre" => "Lorena" "apellidos" => "Álvarez-Rodríguez" ] 1 => array:2 [ "nombre" => "Marcos" "apellidos" => "López-Hoyos" ] 2 => array:2 [ "nombre" => "Eugenio" "apellidos" => "Carrasco-Marín" ] 3 => array:2 [ "nombre" => "Cristina" "apellidos" => "Mata" ] 4 => array:2 [ "nombre" => "Jaime" "apellidos" => "Calvo-Alén" ] 5 => array:2 [ "nombre" => "Elena" "apellidos" => "Aurrecoechea" ] 6 => array:2 [ "nombre" => "Ricardo" "apellidos" => "Blanco" ] 7 => array:2 [ "nombre" => "Teresa" "apellidos" => "Ruiz" ] 8 => array:2 [ "nombre" => "Pedro" "apellidos" => "Muñoz Cacho" ] 9 => array:2 [ "nombre" => "Ignacio" "apellidos" => "Villa" ] 10 => array:2 [ "nombre" => "Víctor Manuel" "apellidos" => "Martínez-Taboada" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173574312000962" "doi" => "10.1016/j.reumae.2012.07.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574312000962?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X12001325?idApp=UINPBA00004M" "url" => "/1699258X/0000000800000006/v1_201305061930/S1699258X12001325/v1_201305061930/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173574312001591" "issn" => "21735743" "doi" => "10.1016/j.reumae.2012.10.003" "estado" => "S300" "fechaPublicacion" => "2012-11-01" "aid" => "455" "copyright" => "Elsevier España, S.L." 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The data of positive and negative affect in the case of educational level are shown as box plots where the line inside the box represents the median, and the lower and upper edges of the boxes represent the 25th and 75th percentiles, respectively, and upper and lower lines outside the boxes represent the 5 and 95 percentiles, respectively. The circles represent outliers. In the case of age, the point cloud represents the estimated regression line with the lfit command of Stata 10.1." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Karina Silva Luna, Ana M. Ortiz, Esther Patiño, Carmen Aguilera, Teresa Velasco, Rosario García de Vicuña, Isidoro González-Alvaro" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Karina" "apellidos" => "Silva Luna" ] 1 => array:2 [ "nombre" => "Ana M." 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Triplicate cultures of 4×106 U-937 cells in the presence of MLIF, LPS or both were harvested at 0.3, 1, 2, 4, 6, 8 and 10h. RNA was obtained from pellets and used for real time PCR. Comparative expression was established using unstimulated cells as reference. LPS induced a strong up-regulation of IL-1β which peaks at 4h. MLIF per se did not affect IL-1β basal expression but MLIF was able to reduce significantly the stimulatory effect of LPS when amebic peptide was added simultaneously to LPS (p=0.05). Bars of SEM are <1 in all points." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan R. Velázquez, Lizeth Garibay-Martínez, Pedro Martínez-Tejada, Yelda A. Leal" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Juan R." "apellidos" => "Velázquez" ] 1 => array:2 [ "nombre" => "Lizeth" "apellidos" => "Garibay-Martínez" ] 2 => array:2 [ "nombre" => "Pedro" "apellidos" => "Martínez-Tejada" ] 3 => array:2 [ "nombre" => "Yelda A." 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Data is presented separately for active giant cell arteritis (GCA, n=55; superior panel) and polymyalgia rheumatica (PMR, n=120; inferior panel)." ] ] ] "textoCompleto" => "IntroductionThe aging process is accompanied by qualitative and quantitative changes in the immune system, which are grouped under the term immunesenesence.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Consequently, the elderly show increased susceptibility to neoplasms, infections, and autoimmune diseases.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> In this sense, aging is accompanied by the appearance of some age-related diseases, and one of the best examples is giant cell arteritis (GCA), a granulomatous systemic vasculitis with a preference for large and medium caliber arteries.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> The clinical manifestations of cranial GCA symptoms ranges from the classic aortic arch syndrome or less specific manifestations such as fever, weight loss or polymyalgia syndrome.<a class="elsevierStyleCrossRefs" href="#bib0020">4–7</a> Polymyalgia rheumatica (PMR) is a syndrome characterized by pain and stiffness of the neck, pelvic girdle and also affects only elderly individuals.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Although PMR occurs normally in the absence of GCA, some patients may also develop arteritis during the disease.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Moreover, it has been suggested that PMR and rheumatoid arthritis in the elderly (Eora), especially the seronegative variety, have much in common.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>The T cell-derived cytokine profile of inflammatory diseases associated with aging suggests that it is primarily mediated by a Th1 response. This may be due to an increase in Th1 cytokine expression, such as IFN-γ that plays a crucial role in the development of GCA,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> or in a defect in regulation by activated Th2 cytokines.In recent years there have been numerous studies of cytokine gene polymorphisms in PMR and GCA.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> However, these studies have focused on pro-inflammatory cytokines rather than Th1 and Th2 cytokines. Th2 immune response is characterized by expression of IL-4, IL-5, IL-9, and IL-13. Theoretically a decrease in the activity of these Th2 cytokines may be accompanied by greater severity of these diseases while Th2 increased activity could be associated with a milder clinical picture. There is only one previous study conducted by Amoli et al.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> in which there was a marginally significant association between GCA and some IL-4 single nucleotide genetic polymorphisms (SNPs).IL-13 is an immunoregulatory protein produced mainly by activated Th2 cells<a class="elsevierStyleCrossRef" href="#bib0070">14</a> and is involved in the maturation and differentiation of B cells. It promotes expression of CD23 and class histocompatibility molecules, IL<a class="elsevierStyleCrossRef" href="#bib0075">15</a> and isotype switching to IgE in B cells.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Furthermore, IL-13 decreases the activity of macrophages, thus inhibiting production of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, among others. Recently, numerous polymorphisms in the gene for IL-13 have been identified and have been associated with IgE levels and/or allergic diseases.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> One of the SNPs located in exon 4 at position 2044 (switch from G to A, denominated G2044A) causes a change of the amino acid (arginine for glutamine at codon 130, denominated R130Q) and possibly affects ligand-receptor interaction.<a class="elsevierStyleCrossRefs" href="#bib0090">18,19</a>The aim of this study was to investigate the association between the R130Q polymorphism of the gene for IL-13 and susceptibility to GCA and 2 other inflammatory diseases associated with aging such as PMR and Eora.Patients and MethodsPatientsThis study included 78 patients with GCA, 174 patients with PMR and 90 patients with Eora (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The control group included 465 healthy individuals recruited from the same region who showed no evidence of the diseases listed above. Both patients and controls were Caucasians of Spanish ancestry and residing in the same geographic area in northern Spain, Cantabria. The sampling and studies were conducted after obtaining written informed consent and the study was approved by the regional Ethics Committee.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>All GCA patients fulfilled the 1990 American College of Rheumatology classification criteria for GCA.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> As shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, 82.7% of patients had characteristic histological evidence for GCA in temporal artery biopsies.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> Patients with PMR were diagnosed according to the criteria proposed by Chuang et al.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> We also included in the study patients with PMR with ESR <40mm/1h but who met the other clinical criteria.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Patients with rheumatoid arthritis (RA) met the 1987 ACR criteria for RA.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> Elderly onset RA was considered if symptoms of the disease began at age 60 or older.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> One third of patients with Eora were rheumatoid factor (RF) positive (280.3±509.7IU/ml) and 25% were positive for anti-cyclic citrullinated peptide (APCC) antibodies (1012±623U/ml).Data was collected by reviewing medical records of PMR patients and gathered clinical features at diagnosis and during follow-up, CRP and ESR at diagnosis and the initial dose of prednisone. The patients were grouped according to the presence or absence of polymyalgia syndrome and the presence or absence of ischemic events. The ischemic events were defined as the presence of visual loss, jaw claudication, stroke, and/or aortic arc syndromes.<a class="elsevierStyleCrossRefs" href="#bib0020">4,7</a> In patients with more than 2 years of follow-up we included analysis of variables such as relapse, duration of treatment with corticosteroids (CS), and cumulative dose of prednisone.<a class="elsevierStyleCrossRefs" href="#bib0025">5,8,25</a> In patients with GCA and PMR we assessed the severity of the disease in terms of the presence of relapses and/or recurrences, duration of corticosteroid treatment and its cumulative dose. In patients with Eora we did not systematically assess the severity of the disease.At diagnosis, patients with isolated PMR received an initial dose of prednisone of 10mg/day (5mg/12h). GCA patients received an initial dose of prednisone between 40 and 60mg/day. Those with ischemic complications also received 31g IV pulses of methylprednisolone/day. The reduction in steroid treatment was individualized according to medical judgment.Genotyping of the R130Q Polymorphism of the IL-13 GeneThe genomic DNA of the individuals studied was extracted from blood using a DNA purification kit (Gentra, GENERATION® DNA Purification kits, MN, USA). The IL13 rs20541 (R130Q) polymorphism<a class="elsevierStyleCrossRef" href="#bib0090">18</a> was determined by gene amplification using 2 primers: sense 5′-CTTCCGTGAGGACTGAATGAGACGGTC-3′ and antisense 5′-GCAAATAATGATGCTTTCGAAGTTTCAGTGGA-3′. The amplification conditions were 4min at 94°C, 1min at 69°C, and 2min at 72°C, and then subjected to 35 cycles of 30s at 94°C, 45s at 67°C, and 30s at 72°C, 5min for extension at 72° C. The PCR products were digested by addition of 0.25U NlaIV and incubation at 37°C for 3.30h. The expected size fragments after digestion in the normal genotype was 210 base pairs (bp) and 26bp, whereas the mutant allele was determined by the presence of 3 bands of 178, 32, and 26bp.Quantification of Serum IL-13Determining the concentration of IL-13 in serum was performed using ELISA. The serum was collected and stored at −80°C until analysis. Serum levels of IL-13 were determined by an ELISA kit (Pelikine Compact Human IL-13, Sanquin, Amsterdam, The Netherlands). The detection limit was 3pg/ml.Statistical AnalysisStatistical analysis of data was performed using SPSS 15.0 (Chicago, IL, USA). The association between PMR and GCA or Eora and the alleles or genotypes of the IL-13 gene was estimated using odds ratios (OR) and confidence intervals at 95% (CI). The frequencies of alleles and genotypes were compared using the chi-square test. To assess differences between groups in the case of numerical variables, we used the Mann–Whitney and Kruskal–Wallis tests as indicated. Differences were considered significant when the P value was <.05.ResultsDemographic and Clinical CharacteristicsThe main demographic, clinical, and laboratory characteristics of different populations are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Most patients with GCA had a positive temporal artery biopsy. Half of patients had ischemic GCA complications. In addition, patients with GCA had higher levels of ESR and CRP compared with patients with PMR and Eora. We found no statistically significant differences between ESR and CRP between PMR and Eora.The R130Q Polymorphism of the Gene for IL-13 Is Associated With Susceptibility to Giant Cell ArteritisThe allelic distributions of the study populations were in Hardy–Weinberg equilibrium, except for patients with PMR (P=.025). Allelic and genotypic distributions of the R130Q IL-13 gene polymorphism in different groups of patients compared with controls are shown in <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2–4</a>. Patients with GCA showed a higher frequency of AA genotype and allele A and a carrier of this allele compared with the control group (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). There were no significant differences in the distribution of the R130Q polymorphism of the IL-13 gene among patients with PMR or Eora and healthy controls (<a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 4</a>). When comparing the different diseases with each other, we find no significant difference between them (Supplementary Tables 1, 2, and 3). When analyzing the 3 age-related pathologies together (Supplementary Table 4) we observed a similar trend to that observed in patients with GCA.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Supplementary material associated with this article can be found in the online version available at <a href="doi:10.1016/j.reumae.2012.07.003">http://dx.doi.org/10.1016/j.reumae.2012.07.003</a>.<elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia><elsevierMultimedia ident="upi0015"></elsevierMultimedia><elsevierMultimedia ident="upi0020"></elsevierMultimedia>Serum Levels of IL-13 in Patients With Chronic Inflammatory Conditions are Associated With Aging and With IL-13 Gene PolymorphismSince the study focuses on the analysis of a polymorphism in the gene for IL-13 we analyzed the differences in the levels of IL-13 in the serum of patients included in the study (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The data show a nonsignificant increase in the concentration of IL-13 concentration in patients with active Eora with respect to healthy controls and a borderline statistical significance (P=.066) in patients with GCA and PMR. After steroid treatment, the levels decreased in all 3 groups of patients although the Eora group's posttreatment levels remained significantly higher than that of GCA and PMR (GCA post vs Eora post P=.037 and PMR post vs Eora post P=.024).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Since the R130Q polymorphism induces a functional amino acid change, we wanted to analyze the impact of this polymorphism in the serum concentration of IL-13 in different patient groups. Since the R130Q polymorphism was very rare, data was not significant, although there was a trend toward decreased levels of serum IL-13 in healthy subjects compared to AA and GG GA. The same trend was also observed in patients with GCA and Eora. In contrast, patients with PMR and the AA genotype showed higher levels of circulating IL-13 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). When we analyzed the 3 groups of patients together there were no significant differences in levels of circulating IL-13 for the different genotypes (<a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3 and 4</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>Studies of Association Between the Polymorphism of IL-13 and Circulating Levels of IL-13 With the Clinical Manifestations and Prognosis in Patients With Giant Cell Arteritis and Polymyalgia RheumaticaTo evaluate the influence of both the genotype of IL-13 as studied and circulating levels of IL-13 in different clinical subgroups, we analyzed patients with GCA according to presence or absence of ischemic signs or polymyalgia syndrome and the PMR patients according to ESR levels (“low” or less than 40mm/1sth and “classic” or greater than 40mm/1sth), and patients were subdivided by the polymyalgic Eora onset or classic form. Although we did not have detailed information on the activity and prognosis of patients with Eora, we also analyzed the possible influence of genotype on the presence of typical autoantibodies (RF and ACCP) and their titer. We found no significant association between genotype and circulating levels of IL-13 with any of the above variables.We evaluated the prognosis in patients with GCA and PMR by analyzing more than 2 years of follow up for the presence of relapses and/or recurrences, duration of corticosteroid treatment and its cumulative dose. As shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> (top panel), patients with GCA, the GA genotype was associated with a shorter duration of treatment with corticosteroids and a lower cumulative dose of the same, probably due to a lower rate of relapse/recurrence. We found no relationship of these prognostic factors with circulating levels of IL-13.DiscussionIL-13 is an immunoregulatory protein produced mainly by activated Th2 cells<a class="elsevierStyleCrossRef" href="#bib0070">14</a> and is involved in the maturation and differentiation of B cells.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> This cytokine is considered part of the Th2 immune response and a reasonable hypothesis is that the imbalance in the Th1/Th2 balance could be involved in the pathogenesis of chronic diseases associated with age and are the result of a dysfunction in immune system regulation. According to this hypothesis, a genetic predisposition in the expression of genes coding for Th2 cytokines could influence the severity and/or susceptibility of these 3 diseases. There is only one previous study conducted by Amoli et al.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> in which there was a marginally significant association between GCA and some SNPs for IL-4. However, these results were more significant when considering only those patients HLA-DRB1*04, suggesting an interaction between HLA-DRB1 and IL-4 contributing to increased susceptibility for the disease.<a class="elsevierStyleCrossRef" href="#bib0065">13</a>Therefore, taking into consideration the failure of previous studies in determining the influence of Th2 cytokine genes, we analyzed for the first time the influence of the rs20541 (R130Q) polymorphism in the gene encoding the IL-13 in a large series of patients with inflammatory diseases associated with aging.The data shows an association of this polymorphism with susceptibility to GCA. Although the differences found in this study are significant only for patients with GCA, PMR patients show a similar trend. However, the study's statistical power for comparisons in allele frequencies and genotype of patients with PMR is low, ranging between 12% and 34%, so the results should be taken with caution and confirmed in studies containing a higher number of patients. Although this study shows a significant association between the analyzed polymorphism and GCA we cannot exclude that other polymorphisms within this gene or its receptor may be associated with susceptibility and/or severity of these diseases. In fact, the polymorphism studied in this work is more clearly associated with asthma and atopy, especially in children. In contrast, the association of other polymorphisms in the gene for IL-13, such as rs20541 (R130Q), rs1800925 (IL13-1055), and rs2243204 have been described in other inflammatory rheumatic disease, which we did not evaluate.<a class="elsevierStyleCrossRefs" href="#bib0130">26–28</a>Moreover, SNPs may have different biological effects depending on the cell type upon which the cytokine acts or the inflammatory environment in which the effect develops.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> In this regard, functional studies conducted in the rs20541 (R130Q) SNP have demonstrated functional consequences on transcriptional activity, increased activity or signaling through its protein, or changes in serum protein levels in different cell types.<a class="elsevierStyleCrossRefs" href="#bib0150">30,31</a> Therefore, in this study we not only investigated the possible genetic association between the R130Q polymorphism and genetic susceptibility to disease but also its correlation with circulating levels of IL-13. It has been suggested that patients homozygous for the mutation of this IL-13 gene exhibit increased levels of circulating IL-1332. It appears that the presence of the AA genotype is associated with decreased levels of serum IL-13 in both healthy controls and in patients with GCA and Eora. In contrast, in PMR this relationship is the opposite, with a higher level of circulating IL-13 in heterozygous subjects, which corresponds to what is published.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> In any case, this data should be taken with caution because of the low frequency of this genotype and the absence of similar studies.Serum and synovial fluid IL-13 have been found increased in patients with various types of arthropathies, including RA.<a class="elsevierStyleCrossRefs" href="#bib0160">32,33</a> In addition, serum levels of IL-13 have been correlated with the presence of autoantibodies, such as RF.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> In our study, although no significant differences with healthy controls were seen, patients with Eora had a tendency to have higher circulating levels of IL-13, which remained despite treatment. Although we found a significant correlation between levels of circulating IL-13 and autoantibody characteristic of RA, our study clearly differs from the above<a class="elsevierStyleCrossRef" href="#bib0165">33</a> in regards to the study population, Eora only, and therefore on the frequency of these autoantibodies.The association of the GA genotype with a lower rate of relapse/recurrence, and therefore with a shorter duration and cumulative dose of corticosteroid treatment in patients with GCA is of interest given the current lack of prognostic markers for this disease, but should be confirmed in a larger series of patients.In summary, the rs20541 (R130Q) polymorphism of the IL13 gene is associated with susceptibility to GCA. The utility of this gene to predict prognosis in GCA should be confirmed in studies with more patients. Further studies are needed regarding Th2 cytokine genes that allow us to clarify this issue.Ethical disclosuresProtection of human and animal subjects. The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.Confidentiality of Data. The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.Right to privacy and informed consent. The authors have obtained the informed consent of the patients and /or subjects mentioned in the article. The author for correspondence is in possession of this document.FinancingThis study has been financed with grants from the Fundación Marqués de Valdecilla-IFIMAV and the Fondo de Investigación Sanitaria (PI050475 and PI080098). Lorena Álvarez-Rodríguez was financed with a research grant from the Fundación Marqués de Valdecilla-IFIMAV. Iñaki Beares and Marta González (financed by the Fundación Marqués de Valdecilla-IFIMAV) and Carolina Santa Cruz (financed through a research grant from Schering-Ploug, Spain).Conflict of InterestNone." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:2 [ "identificador" => "xres125973" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objective" 2 => "Material and methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec113268" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres125974" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Material y métodos" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec113269" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Genotyping of the R130Q Polymorphism of the IL-13 Gene" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Quantification of Serum IL-13" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical Analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Demographic and Clinical Characteristics" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "The R130Q Polymorphism of the Gene for IL-13 Is Associated With Susceptibility to Giant Cell Arteritis" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Serum Levels of IL-13 in Patients With Chronic Inflammatory Conditions are Associated With Aging and With IL-13 Gene Polymorphism" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Studies of Association Between the Polymorphism of IL-13 and Circulating Levels of IL-13 With the Clinical Manifestations and Prognosis in Patients With Giant Cell Arteritis and Polymyalgia Rheumatica" ] ] ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Ethical disclosures" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Financing" ] 10 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflict of Interest" ] 11 => array:2 [ "identificador" => "xack38133" "titulo" => "Acknowledgements" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-04-12" "fechaAceptado" => "2012-04-25" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec113268" "palabras" => array:6 [ 0 => "Interleukin 13" 1 => "Giant cell arteritis" 2 => "Polymyalgia rheumatica" 3 => "Elderly-onset rheumatoid arthritis" 4 => "Polymophism" 5 => "Aging" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec113269" "palabras" => array:6 [ 0 => "Interleucina 13" 1 => "Arteritis de células gigantes" 2 => "Polimialgia reumática" 3 => "Artritis reumatoide de inicio en el anciano" 4 => "Polimorfismo" 5 => "Envejecimiento" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo investigate whether there is association between the rs20541 (R130Q) polymorphism in the IL-13 gene with disease susceptibility and clinical subsets in patients with elderly-associated inflammatory chronic diseases. Material and methodsSeventy-eight patients with giant cell arteritis (GCA), 174 with polymyalgia rheumatica (PMR), 90 elderly-onset rheumatoid arthritis (EORA), and 465 healthy controls from the same geographic area were studied. The rs20541 (R130Q) polymorphism in the IL-13 gene was evaluated by PCR-RFLP. Circulating levels of IL-13 were measured by ELISA. ResultsA higher frequency of the AA genotype [2.349 (0.994–5.554)], as well as the allele A [1.589 (1.085–2.328] and the A carriers [1.656 (1.021–2.686)] (P<.05) was observed in the GCA patients. No significant differences were observed in the PMR and EORA patients as compared with the healthy controls. Neither difference was observed among the different disease groups studied. In GCA patients, differences in the genotype were associated with a worse prognosis. In PMR patients, the AA genotype was associated with higher levels of serum IL-13 than the GA one. However, such an association was not detected for controls and the other disease groups. ConclusionsGCA is more frequent in carriers of the rs20541 (R130Q) polymorphism in the IL-13 gene. The utility of this polymorphism to predict the GCA prognosis must be confirmed in studies with a higher number of patients." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "ObjetivoInvestigar si existe asociación del polimorfismo rs20541 (R130Q) del gen de la IL-13 con la susceptibilidad y la expresión clínica de pacientes con enfermedades inflamatorias crónicas asociadas al envejecimiento. Material y métodosSe estudiaron 78 pacientes con arteritis de células gigantes (ACG), 174 con polimialgia reumática (PMR), 90 con artritis reumatoide de comienzo en el anciano (EORA), y 465 controles sanos de la misma zona geográfica. El polimorfismo rs20541 (R130Q) para IL-13 se evaluó mediante PCR-RFLP. Los niveles de IL-13 circulante se determinaron por ELISA. ResultadosEn los pacientes con ACG se observó una mayor frecuencia del genotipo AA [2,349 (0,994-5,554)], así como del alelo A [1,589 (1,085-2,328)] y de portadores de dicho alelo [1,656 (1,021-2,686)] (p<0,05). No encontramos diferencias significativas entre los pacientes con PMR y EORA respecto al grupo control. Cuando comparamos las diferentes patologías entre sí, tampoco encontramos diferencias significativas entre ellas. En los pacientes con ACG las diferencias en el genotipo se asociaron con el pronóstico de la enfermedad. En pacientes con PMR, el genotipo AA se asoció con niveles más elevados de IL-13 circulante comparado con el GA. Sin embargo, esta asociación no se apreció para los controles o las otras enfermedades. ConclusionesLa ACG es más frecuente en individuos portadores del polimorfismo rs20541 (R130Q) del gen de la IL13. La utilidad de este gen para predecir el pronóstico en ACG debe ser confirmada en estudios con mayor número de pacientes." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Álvarez-Rodríguez L, et al. Análisis del polimorfismo rs20541 (R130Q) del gen de la IL-13 en pacientes con enfermedades inflamatorias crónicas asociadas al envejecimiento. Reumatol Clin. 2012;8:321–7." ] ] "multimedia" => array:12 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1472 "Ancho" => 1383 "Tamanyo" => 86945 ] ] "descripcion" => array:1 [ "en" => "Serum concentration of IL-13 in patients with giant cell arteritis (GCA), polymyalgia rheumatic (PRM) and elderly onset rheumatoid arthritis (EORA) in comparison to healthy controls (HC) paired for age and gender. Results are expressed as boxplots with a median and interquartile range for each group. Data was obtained in the active phase of the disease (pre) and in remission after steroid treatment (post). The number of subjects in each group and the statistical significance when P was under .05 is shown." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 831 "Ancho" => 2249 "Tamanyo" => 84118 ] ] "descripcion" => array:1 [ "en" => "Serum concentration of IL-13 in relation to SNP R130Q of the IL-13 gene. Data is presented separately for patients with active giant cell arteritis (GCA; No.=15), polymyalgia rheumatica (PMR; No.=71) and elderly onset rheumatoid arthritis (EORA; No.=28) and healthy controls paired by age and gender (HC; No.=21)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2057 "Ancho" => 2961 "Tamanyo" => 258109 ] ] "descripcion" => array:1 [ "en" => "Duration in months of steroid treatment (CS, left), cumulative steroid dose (in middle) and number of relapses (right) in relation to the SNP R130Q of the IL-13 gene. Data is presented separately for active giant cell arteritis (GCA, n=55; superior panel) and polymyalgia rheumatica (PMR, n=120; inferior panel)." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1409 "Ancho" => 1409 "Tamanyo" => 42305 ] ] "descripcion" => array:1 [ "en" => "Serum IL-13 concentrations in relation to the SNP R130Q of the IL-13 gene. Data is presented jointly for patients with active disease in any of the 3 cases (No. total=114: giant cell arteritis [GCA; No.=15], polymyalgia rheumatica [PMR; No.=71] and elderly onset rheumatoid arthritis [EORA; No.=28])." ] ] 4 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "SD: standard deviation; CRP: C reactive protein; ESR: erythrosedimentation rate." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">GCA (n=78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">PMR (n=174) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">EORA (n=90) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Women, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age at diagnosis (mean±SD, years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73.7±7.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.9±7.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70.4±7.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive biopsy/total number of temporal artery biopsies performed, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62/75 (82.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0/64 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0/2 (0%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ischemic manifestations, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VESRSG (mean±SD, mm/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86.4±32.9<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.6±30.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66.8±34.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CRP (mean±SD, mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.7±5.6<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.7±5.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.3±5.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Follow up time (mean±SD, months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65.6±47.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.8±45.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.1±69.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212481.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "GCA vs PMR: P≤.001 both for ESR and CRP." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "GCA vs EORA: P=.004 for ESR and P=.021 for CRP." ] ] ] "descripcion" => array:1 [ "en" => "Demographic, Clinical and Laboratory Characteristics of Patients With Giant Cell Arteritis (GCA), Polymyalgia Rheumatica (PMR) and Elderly Onset Rheumatoid Arthritis (EORA) Included in the Study." ] ] 5 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genotype \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ACG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OR (95% CI) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n=465 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n=78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-13 [db SNP ID rs20541 (R130Q)]</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genotype frequency</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">301/465 (64.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41/78 (52.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reference \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">139/465 (29.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29/78 (37.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.104 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.532 (0.914–2.567) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25/465 (5.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">08/78 (10.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.046 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.349 (0.994–5.554) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allelic frequency</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">741/930 (79.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">111/156 (71.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reference \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">189/930 (20.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45/156 (28.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.017 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.589 (1.085–2.328) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequency of allelic carriers</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allele G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">440/465 (94.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70/78 (89.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.095 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.497 (0.216–1.146) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allele A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">164/465 (35.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37/78 (47.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.039 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.656 (1.021–2.686) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212480.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Allelic and Genotype Frequencies of the rs20541 (R130Q) Polymorphism of the Il-13 Gene in Patients With Giant Cell Arteritis (GCA) Compared to Healthy Controls." ] ] 6 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genotype \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PMR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OR (95% CI) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n=465 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n=174 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-13 [db SNP ID rs20541 (R130Q)]</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genotype frequency</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">301/465 (64.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">107/174 (61.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reference \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">139/465 (29.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52/174 (29.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.796 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.052 (0.714–1.550) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25/465 (5.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15/174 (8.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.126 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.688 (0.858–3.322) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allelic frequency</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">741/930 (79.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">266/348 (76.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reference \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">189/930 (20.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82/348 (23.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.207 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.209 (0.900–1.623) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequency of allelic carriers</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allele G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">440/465 (94.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">159/174 (91.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.132 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.602 (0.310–1.171) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allele A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">164/465 (35.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67/174 (38.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.448 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.149 (0.802–1.647) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212483.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Allelic and Genotypical Frequencies of the rs20541 (R130Q) Polymorphism of the IL-13 Gene in Patients With Polymyalgia Rheumatica (PMR) Compared to Healthy Controls." ] ] 7 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genotype \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EORA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OR (95% CI) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n=465 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n=90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL-13 [db SNP ID rs20541 (R130Q)]</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genotype frequency</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">301/465 (64.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50/90 (55.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reference \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">139/465 (29.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36/90 (40.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.065 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.559 (0.971–2.503) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25/465 (5.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">04/90 (4.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.947 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.963 (0.322–2.885) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allelic frequency</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">741/930 (79.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">136/180 (75.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reference \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">189/930 (20.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44/180 (24.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.214 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.268 (0.871–1.847) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequency of allelic carriers</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allele G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">440/465 (94.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86/90 (95.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.716 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.222 (0.415–3.599) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allele A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">164/465 (35.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40/90 (44.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.098 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.468 (0.929–2.319) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab212482.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Allelic and Genotypical Frequencies of the rs20541 (R130Q) Polymorphism of the Il-13 Gene in Patients With Elderly Onset Rheumatoid Arthritis (EORA) Compared to Healthy Controls." ] ] 8 => array:7 [ "identificador" => "upi0005" "etiqueta" => "Supplementary Table 1" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.doc" "ficheroTamanyo" => 45568 ] "descripcion" => array:1 [ "en" => "Allelic and genotypic frequencies of the IL-13 rs20541 (R130Q) gene polymorphism in patients with Giant Cell Arteritis (GCA) compared to Polymyalgia Rheumatica (PMR)." ] ] 9 => array:7 [ "identificador" => "upi0010" "etiqueta" => "Supplementary Table 2" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc2.doc" "ficheroTamanyo" => 47104 ] "descripcion" => array:1 [ "en" => "Allelic and genotypic frequencies of the IL-13 rs20541 (R130Q) gene polymorphism in patients with Giant Cell Arteritis (GCA) compared to Elderly onset rheumatoid arthritis (EORA)." ] ] 10 => array:7 [ "identificador" => "upi0015" "etiqueta" => "Supplementary Table 3" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc3.doc" "ficheroTamanyo" => 47104 ] "descripcion" => array:1 [ "en" => "Allelic and genotypic frequencies of the IL-13 rs20541 (R130Q) gene polymorphism in patients with Elderly onset rheumatoid arthritis (EORA) compared with Polymyalgia rheumatica (PMR)." ] ] 11 => array:7 [ "identificador" => "upi0020" "etiqueta" => "Supplementary Table 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We would also like to thank all of the physicians from the Rheumatology Department who have monitored patients and thank both patients and controls for their participation in the study." ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000000800000006/v1_201305061648/S2173574312000962/v1_201305061648/en/main.assets" "Apartado" => array:4 [ "identificador" => "17338" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Original Article" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000000800000006/v1_201305061648/S2173574312000962/v1_201305061648/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574312000962?idApp=UINPBA00004M"]

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Original Article

Analysis of the rs20541 (R130Q) Polymorphism in the IL-13 Gene in Patients With Elderly-associated Chronic Inflammatory Diseases

Análisis del polimorfismo rs20541 (R130Q) del gen de la IL-13 en pacientes con enfermedades inflamatorias crónicas asociadas al envejecimiento

Lorena Álvarez-Rodrígueza, Marcos López-Hoyosb, Eugenio Carrasco-Marínb, Cristina Matac, Jaime Calvo-Alénc, Elena Aurrecoecheac, Ricardo Blancoa, Teresa Ruizc, Pedro Muñoz Cachod, Ignacio Villac, Víctor Manuel Martínez-Taboadaa,

Corresponding author

vmartinezt@medynet.com

Corresponding author.

a Servicio de Reumatología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Facultad de Medicina, Universidad de Cantabria, Santander, Spain

b Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Facultad de Medicina, Universidad de Cantabria, Santander, Spain

c Sección de Reumatología, Hospital de Sierrallana, Torrelavega, Cantabria, Spain

d Gerencia Atención Primaria, Servicio Cántabro de Salud, Cantabria, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The aging process is accompanied by qualitative and quantitative changes in the immune system&#44; which are grouped under the term immunesenesence&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Consequently&#44; the elderly show increased susceptibility to neoplasms&#44; infections&#44; and autoimmune diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In this sense&#44; aging is accompanied by the appearance of some age-related diseases&#44; and one of the best examples is giant cell arteritis &#40;GCA&#41;&#44; a granulomatous systemic vasculitis with a preference for large and medium caliber arteries&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The clinical manifestations of cranial GCA symptoms ranges from the classic aortic arch syndrome or less specific manifestations such as fever&#44; weight loss or polymyalgia syndrome&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;7</span></a> Polymyalgia rheumatica &#40;PMR&#41; is a syndrome characterized by pain and stiffness of the neck&#44; pelvic girdle and also affects only elderly individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Although PMR occurs normally in the absence of GCA&#44; some patients may also develop arteritis during the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Moreover&#44; it has been suggested that PMR and rheumatoid arthritis in the elderly &#40;Eora&#41;&#44; especially the seronegative variety&#44; have much in common&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The T cell-derived cytokine profile of inflammatory diseases associated with aging suggests that it is primarily mediated by a Th1 response&#46; This may be due to an increase in Th1 cytokine expression&#44; such as IFN-&#947; that plays a crucial role in the development of GCA&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> or in a defect in regulation by activated Th2 cytokines&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In recent years there have been numerous studies of cytokine gene polymorphisms in PMR and GCA&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> However&#44; these studies have focused on pro-inflammatory cytokines rather than Th1 and Th2 cytokines&#46; Th2 immune response is characterized by expression of IL-4&#44; IL-5&#44; IL-9&#44; and IL-13&#46; Theoretically a decrease in the activity of these Th2 cytokines may be accompanied by greater severity of these diseases while Th2 increased activity could be associated with a milder clinical picture&#46; There is only one previous study conducted by Amoli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> in which there was a marginally significant association between GCA and some IL-4 single nucleotide genetic polymorphisms &#40;SNPs&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">IL-13 is an immunoregulatory protein produced mainly by activated Th2 cells<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and is involved in the maturation and differentiation of B cells&#46; It promotes expression of CD23 and class histocompatibility molecules&#44; IL<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and isotype switching to IgE in B cells&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Furthermore&#44; IL-13 decreases the activity of macrophages&#44; thus inhibiting production of pro-inflammatory cytokines such as IL-1&#946;&#44; IL-6&#44; and TNF-&#945;&#44; among others&#46; Recently&#44; numerous polymorphisms in the gene for IL-13 have been identified and have been associated with IgE levels and&#47;or allergic diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> One of the SNPs located in exon 4 at position 2044 &#40;switch from G to A&#44; denominated G2044A&#41; causes a change of the amino acid &#40;arginine for glutamine at codon 130&#44; denominated R130Q&#41; and possibly affects ligand-receptor interaction&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of this study was to investigate the association between the R130Q polymorphism of the gene for IL-13 and susceptibility to GCA and 2 other inflammatory diseases associated with aging such as PMR and Eora&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patients and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">This study included 78 patients with GCA&#44; 174 patients with PMR and 90 patients with Eora &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The control group included 465 healthy individuals recruited from the same region who showed no evidence of the diseases listed above&#46; Both patients and controls were Caucasians of Spanish ancestry and residing in the same geographic area in northern Spain&#44; Cantabria&#46; The sampling and studies were conducted after obtaining written informed consent and the study was approved by the regional Ethics Committee&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">All GCA patients fulfilled the 1990 American College of Rheumatology classification criteria for GCA&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> As shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; 82&#46;7&#37; of patients had characteristic histological evidence for GCA in temporal artery biopsies&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Patients with PMR were diagnosed according to the criteria proposed by Chuang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> We also included in the study patients with PMR with ESR &#60;40<span class="elsevierStyleHsp" style=""></span>mm&#47;1<span class="elsevierStyleHsp" style=""></span>h but who met the other clinical criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Patients with rheumatoid arthritis &#40;RA&#41; met the 1987 ACR criteria for RA&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Elderly onset RA was considered if symptoms of the disease began at age 60 or older&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> One third of patients with Eora were rheumatoid factor &#40;RF&#41; positive &#40;280&#46;3&#177;509&#46;7<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#41; and 25&#37; were positive for anti-cyclic citrullinated peptide &#40;APCC&#41; antibodies &#40;1012&#177;623<span class="elsevierStyleHsp" style=""></span>U&#47;ml&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Data was collected by reviewing medical records of PMR patients and gathered clinical features at diagnosis and during follow-up&#44; CRP and ESR at diagnosis and the initial dose of prednisone&#46; The patients were grouped according to the presence or absence of polymyalgia syndrome and the presence or absence of ischemic events&#46; The ischemic events were defined as the presence of visual loss&#44; jaw claudication&#44; stroke&#44; and&#47;or aortic arc syndromes&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;7</span></a> In patients with more than 2 years of follow-up we included analysis of variables such as relapse&#44; duration of treatment with corticosteroids &#40;CS&#41;&#44; and cumulative dose of prednisone&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;8&#44;25</span></a> In patients with GCA and PMR we assessed the severity of the disease in terms of the presence of relapses and&#47;or recurrences&#44; duration of corticosteroid treatment and its cumulative dose&#46; In patients with Eora we did not systematically assess the severity of the disease&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">At diagnosis&#44; patients with isolated PMR received an initial dose of prednisone of 10<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; GCA patients received an initial dose of prednisone between 40 and 60<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; Those with ischemic complications also received 31<span class="elsevierStyleHsp" style=""></span>g IV pulses of methylprednisolone&#47;day&#46; The reduction in steroid treatment was individualized according to medical judgment&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Genotyping of the R130Q Polymorphism of the IL-13 Gene</span><p id="par0050" class="elsevierStylePara elsevierViewall">The genomic DNA of the individuals studied was extracted from blood using a DNA purification kit &#40;Gentra&#44; GENERATION<span class="elsevierStyleSup">&#174;</span> DNA Purification kits&#44; MN&#44; USA&#41;&#46; The IL13 rs20541 &#40;R130Q&#41; polymorphism<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> was determined by gene amplification using 2 primers&#58; sense 5&#8242;-CTTCCGTGAGGACTGAATGAGACGGTC-3&#8242; and antisense 5&#8242;-GCAAATAATGATGCTTTCGAAGTTTCAGTGGA-3&#8242;&#46; The amplification conditions were 4<span class="elsevierStyleHsp" style=""></span>min at 94<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 1<span class="elsevierStyleHsp" style=""></span>min at 69<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; and 2<span class="elsevierStyleHsp" style=""></span>min at 72<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; and then subjected to 35 cycles of 30<span class="elsevierStyleHsp" style=""></span>s at 94<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 45<span class="elsevierStyleHsp" style=""></span>s at 67<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; and 30<span class="elsevierStyleHsp" style=""></span>s at 72<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 5<span class="elsevierStyleHsp" style=""></span>min for extension at 72<span class="elsevierStyleHsp" style=""></span>&#176; C&#46; The PCR products were digested by addition of 0&#46;25<span class="elsevierStyleHsp" style=""></span>U NlaIV and incubation at 37<span class="elsevierStyleHsp" style=""></span>&#176;C for 3&#46;30<span class="elsevierStyleHsp" style=""></span>h&#46; The expected size fragments after digestion in the normal genotype was 210 base pairs &#40;bp&#41; and 26<span class="elsevierStyleHsp" style=""></span>bp&#44; whereas the mutant allele was determined by the presence of 3 bands of 178&#44; 32&#44; and 26<span class="elsevierStyleHsp" style=""></span>bp&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Quantification of Serum IL-13</span><p id="par0055" class="elsevierStylePara elsevierViewall">Determining the concentration of IL-13 in serum was performed using ELISA&#46; The serum was collected and stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C until analysis&#46; Serum levels of IL-13 were determined by an ELISA kit &#40;Pelikine Compact Human IL-13&#44; Sanquin&#44; Amsterdam&#44; The Netherlands&#41;&#46; The detection limit was 3<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical Analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Statistical analysis of data was performed using SPSS 15&#46;0 &#40;Chicago&#44; IL&#44; USA&#41;&#46; The association between PMR and GCA or Eora and the alleles or genotypes of the IL-13 gene was estimated using odds ratios &#40;OR&#41; and confidence intervals at 95&#37; &#40;CI&#41;&#46; The frequencies of alleles and genotypes were compared using the chi-square test&#46; To assess differences between groups in the case of numerical variables&#44; we used the Mann&#8211;Whitney and Kruskal&#8211;Wallis tests as indicated&#46; Differences were considered significant when the <span class="elsevierStyleItalic">P</span> value was &#60;&#46;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Demographic and Clinical Characteristics</span><p id="par0065" class="elsevierStylePara elsevierViewall">The main demographic&#44; clinical&#44; and laboratory characteristics of different populations are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Most patients with GCA had a positive temporal artery biopsy&#46; Half of patients had ischemic GCA complications&#46; In addition&#44; patients with GCA had higher levels of ESR and CRP compared with patients with PMR and Eora&#46; We found no statistically significant differences between ESR and CRP between PMR and Eora&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">The R130Q Polymorphism of the Gene for IL-13 Is Associated With Susceptibility to Giant Cell Arteritis</span><p id="par0070" class="elsevierStylePara elsevierViewall">The allelic distributions of the study populations were in Hardy&#8211;Weinberg equilibrium&#44; except for patients with PMR &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;025&#41;&#46; Allelic and genotypic distributions of the R130Q IL-13 gene polymorphism in different groups of patients compared with controls are shown in <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2&#8211;4</a>&#46; Patients with GCA showed a higher frequency of AA genotype and allele A and a carrier of this allele compared with the control group &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; There were no significant differences in the distribution of the R130Q polymorphism of the IL-13 gene among patients with PMR or Eora and healthy controls &#40;<a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 4</a>&#41;&#46; When comparing the different diseases with each other&#44; we find no significant difference between them &#40;Supplementary Tables 1&#44; 2&#44; and 3&#41;&#46; When analyzing the 3 age-related pathologies together &#40;Supplementary Table 4&#41; we observed a similar trend to that observed in patients with GCA&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewcompact-standard">Supplementary material associated with this article can be found in the online version available at <a href="doi:10.1016/j.reumae.2012.07.003">http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;reumae&#46;2012&#46;07&#46;003</a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewextended"><elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia><elsevierMultimedia ident="upi0015"></elsevierMultimedia><elsevierMultimedia ident="upi0020"></elsevierMultimedia></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Serum Levels of IL-13 in Patients With Chronic Inflammatory Conditions are Associated With Aging and With IL-13 Gene Polymorphism</span><p id="par0085" class="elsevierStylePara elsevierViewall">Since the study focuses on the analysis of a polymorphism in the gene for IL-13 we analyzed the differences in the levels of IL-13 in the serum of patients included in the study &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The data show a nonsignificant increase in the concentration of IL-13 concentration in patients with active Eora with respect to healthy controls and a borderline statistical significance &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;066&#41; in patients with GCA and PMR&#46; After steroid treatment&#44; the levels decreased in all 3 groups of patients although the Eora group&#39;s posttreatment levels remained significantly higher than that of GCA and PMR &#40;GCA post vs Eora post <span class="elsevierStyleItalic">P</span>&#61;&#46;037 and PMR post vs Eora post <span class="elsevierStyleItalic">P</span>&#61;&#46;024&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Since the R130Q polymorphism induces a functional amino acid change&#44; we wanted to analyze the impact of this polymorphism in the serum concentration of IL-13 in different patient groups&#46; Since the R130Q polymorphism was very rare&#44; data was not significant&#44; although there was a trend toward decreased levels of serum IL-13 in healthy subjects compared to AA and GG GA&#46; The same trend was also observed in patients with GCA and Eora&#46; In contrast&#44; patients with PMR and the AA genotype showed higher levels of circulating IL-13 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; When we analyzed the 3 groups of patients together there were no significant differences in levels of circulating IL-13 for the different genotypes &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Studies of Association Between the Polymorphism of IL-13 and Circulating Levels of IL-13 With the Clinical Manifestations and Prognosis in Patients With Giant Cell Arteritis and Polymyalgia Rheumatica</span><p id="par0095" class="elsevierStylePara elsevierViewall">To evaluate the influence of both the genotype of IL-13 as studied and circulating levels of IL-13 in different clinical subgroups&#44; we analyzed patients with GCA according to presence or absence of ischemic signs or polymyalgia syndrome and the PMR patients according to ESR levels &#40;&#8220;low&#8221; or less than 40<span class="elsevierStyleHsp" style=""></span>mm&#47;1st<span class="elsevierStyleHsp" style=""></span>h and &#8220;classic&#8221; or greater than 40<span class="elsevierStyleHsp" style=""></span>mm&#47;1st<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; and patients were subdivided by the polymyalgic Eora onset or classic form&#46; Although we did not have detailed information on the activity and prognosis of patients with Eora&#44; we also analyzed the possible influence of genotype on the presence of typical autoantibodies &#40;RF and ACCP&#41; and their titer&#46; We found no significant association between genotype and circulating levels of IL-13 with any of the above variables&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We evaluated the prognosis in patients with GCA and PMR by analyzing more than 2 years of follow up for the presence of relapses and&#47;or recurrences&#44; duration of corticosteroid treatment and its cumulative dose&#46; As shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> &#40;top panel&#41;&#44; patients with GCA&#44; the GA genotype was associated with a shorter duration of treatment with corticosteroids and a lower cumulative dose of the same&#44; probably due to a lower rate of relapse&#47;recurrence&#46; We found no relationship of these prognostic factors with circulating levels of IL-13&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">IL-13 is an immunoregulatory protein produced mainly by activated Th2 cells<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and is involved in the maturation and differentiation of B cells&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> This cytokine is considered part of the Th2 immune response and a reasonable hypothesis is that the imbalance in the Th1&#47;Th2 balance could be involved in the pathogenesis of chronic diseases associated with age and are the result of a dysfunction in immune system regulation&#46; According to this hypothesis&#44; a genetic predisposition in the expression of genes coding for Th2 cytokines could influence the severity and&#47;or susceptibility of these 3 diseases&#46; There is only one previous study conducted by Amoli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> in which there was a marginally significant association between GCA and some SNPs for IL-4&#46; However&#44; these results were more significant when considering only those patients HLA-DRB1&#42;04&#44; suggesting an interaction between HLA-DRB1 and IL-4 contributing to increased susceptibility for the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Therefore&#44; taking into consideration the failure of previous studies in determining the influence of Th2 cytokine genes&#44; we analyzed for the first time the influence of the rs20541 &#40;R130Q&#41; polymorphism in the gene encoding the IL-13 in a large series of patients with inflammatory diseases associated with aging&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The data shows an association of this polymorphism with susceptibility to GCA&#46; Although the differences found in this study are significant only for patients with GCA&#44; PMR patients show a similar trend&#46; However&#44; the study&#39;s statistical power for comparisons in allele frequencies and genotype of patients with PMR is low&#44; ranging between 12&#37; and 34&#37;&#44; so the results should be taken with caution and confirmed in studies containing a higher number of patients&#46; Although this study shows a significant association between the analyzed polymorphism and GCA we cannot exclude that other polymorphisms within this gene or its receptor may be associated with susceptibility and&#47;or severity of these diseases&#46; In fact&#44; the polymorphism studied in this work is more clearly associated with asthma and atopy&#44; especially in children&#46; In contrast&#44; the association of other polymorphisms in the gene for IL-13&#44; such as rs20541 &#40;R130Q&#41;&#44; rs1800925 &#40;IL13-1055&#41;&#44; and rs2243204 have been described in other inflammatory rheumatic disease&#44; which we did not evaluate&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#8211;28</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Moreover&#44; SNPs may have different biological effects depending on the cell type upon which the cytokine acts or the inflammatory environment in which the effect develops&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> In this regard&#44; functional studies conducted in the rs20541 &#40;R130Q&#41; SNP have demonstrated functional consequences on transcriptional activity&#44; increased activity or signaling through its protein&#44; or changes in serum protein levels in different cell types&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a> Therefore&#44; in this study we not only investigated the possible genetic association between the R130Q polymorphism and genetic susceptibility to disease but also its correlation with circulating levels of IL-13&#46; It has been suggested that patients homozygous for the mutation of this IL-13 gene exhibit increased levels of circulating IL-1332&#46; It appears that the presence of the AA genotype is associated with decreased levels of serum IL-13 in both healthy controls and in patients with GCA and Eora&#46; In contrast&#44; in PMR this relationship is the opposite&#44; with a higher level of circulating IL-13 in heterozygous subjects&#44; which corresponds to what is published&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> In any case&#44; this data should be taken with caution because of the low frequency of this genotype and the absence of similar studies&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Serum and synovial fluid IL-13 have been found increased in patients with various types of arthropathies&#44; including RA&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#44;33</span></a> In addition&#44; serum levels of IL-13 have been correlated with the presence of autoantibodies&#44; such as RF&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> In our study&#44; although no significant differences with healthy controls were seen&#44; patients with Eora had a tendency to have higher circulating levels of IL-13&#44; which remained despite treatment&#46; Although we found a significant correlation between levels of circulating IL-13 and autoantibody characteristic of RA&#44; our study clearly differs from the above<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> in regards to the study population&#44; Eora only&#44; and therefore on the frequency of these autoantibodies&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The association of the GA genotype with a lower rate of relapse&#47;recurrence&#44; and therefore with a shorter duration and cumulative dose of corticosteroid treatment in patients with GCA is of interest given the current lack of prognostic markers for this disease&#44; but should be confirmed in a larger series of patients&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In summary&#44; the rs20541 &#40;R130Q&#41; polymorphism of the IL13 gene is associated with susceptibility to GCA&#46; The utility of this gene to predict prognosis in GCA should be confirmed in studies with more patients&#46; Further studies are needed regarding Th2 cytokine genes that allow us to clarify this issue&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Protection of human and animal subjects</span>&#46; The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Confidentiality of Data</span>&#46; The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Right to privacy and informed consent</span>&#46; The authors have obtained the informed consent of the patients and &#47;or subjects mentioned in the article&#46; The author for correspondence is in possession of this document&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Financing</span><p id="par0140" class="elsevierStylePara elsevierViewall">This study has been financed with grants from the <span class="elsevierStyleGrantSponsor" id="gs0005">Fundaci&#243;n Marqu&#233;s de Valdecilla-IFIMAV</span> and the <span class="elsevierStyleGrantSponsor" id="gs0010">Fondo de Investigaci&#243;n Sanitaria</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0005">PI050475</span> and <span class="elsevierStyleGrantNumber" refid="gs0010">PI080098</span>&#41;&#46; Lorena &#193;lvarez-Rodr&#237;guez was financed with a research grant from the <span class="elsevierStyleGrantSponsor">Fundaci&#243;n Marqu&#233;s de Valdecilla-IFIMAV</span>&#46; I&#241;aki Beares and Marta Gonz&#225;lez &#40;financed by the <span class="elsevierStyleGrantSponsor">Fundaci&#243;n Marqu&#233;s de Valdecilla-IFIMAV</span>&#41; and Carolina Santa Cruz &#40;financed through a research grant from <span class="elsevierStyleGrantSponsor">Schering-Ploug&#44; Spain</span>&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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            0 => "Resumen"
            1 => "Objetivo"
            2 => "Material y m&#233;todos"
            3 => "Resultados"
            4 => "Conclusiones"
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec113269"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Patients and Methods"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patients"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Genotyping of the R130Q Polymorphism of the IL-13 Gene"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Quantification of Serum IL-13"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Statistical Analysis"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0035"
          "titulo" => "Results"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Demographic and Clinical Characteristics"
            ]
            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "The R130Q Polymorphism of the Gene for IL-13 Is Associated With Susceptibility to Giant Cell Arteritis"
            ]
            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Serum Levels of IL-13 in Patients With Chronic Inflammatory Conditions are Associated With Aging and With IL-13 Gene Polymorphism"
            ]
            3 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Studies of Association Between the Polymorphism of IL-13 and Circulating Levels of IL-13 With the Clinical Manifestations and Prognosis in Patients With Giant Cell Arteritis and Polymyalgia Rheumatica"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Ethical disclosures"
        ]
        9 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Financing"
        ]
        10 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Conflict of Interest"
        ]
        11 => array:2 [
          "identificador" => "xack38133"
          "titulo" => "Acknowledgements"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2012-04-12"
    "fechaAceptado" => "2012-04-25"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec113268"
          "palabras" => array:6 [
            0 => "Interleukin 13"
            1 => "Giant cell arteritis"
            2 => "Polymyalgia rheumatica"
            3 => "Elderly-onset rheumatoid arthritis"
            4 => "Polymophism"
            5 => "Aging"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec113269"
          "palabras" => array:6 [
            0 => "Interleucina 13"
            1 => "Arteritis de c&#233;lulas gigantes"
            2 => "Polimialgia reum&#225;tica"
            3 => "Artritis reumatoide de inicio en el anciano"
            4 => "Polimorfismo"
            5 => "Envejecimiento"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To investigate whether there is association between the rs20541 &#40;R130Q&#41; polymorphism in the IL-13 gene with disease susceptibility and clinical subsets in patients with elderly-associated inflammatory chronic diseases&#46;</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Seventy-eight patients with giant cell arteritis &#40;GCA&#41;&#44; 174 with polymyalgia rheumatica &#40;PMR&#41;&#44; 90 elderly-onset rheumatoid arthritis &#40;EORA&#41;&#44; and 465 healthy controls from the same geographic area were studied&#46; The rs20541 &#40;R130Q&#41; polymorphism in the IL-13 gene was evaluated by PCR-RFLP&#46; Circulating levels of IL-13 were measured by ELISA&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A higher frequency of the AA genotype &#91;2&#46;349 &#40;0&#46;994&#8211;5&#46;554&#41;&#93;&#44; as well as the allele A &#91;1&#46;589 &#40;1&#46;085&#8211;2&#46;328&#93; and the A carriers &#91;1&#46;656 &#40;1&#46;021&#8211;2&#46;686&#41;&#93; &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41; was observed in the GCA patients&#46; No significant differences were observed in the PMR and EORA patients as compared with the healthy controls&#46; Neither difference was observed among the different disease groups studied&#46; In GCA patients&#44; differences in the genotype were associated with a worse prognosis&#46; In PMR patients&#44; the AA genotype was associated with higher levels of serum IL-13 than the GA one&#46; However&#44; such an association was not detected for controls and the other disease groups&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">GCA is more frequent in carriers of the rs20541 &#40;R130Q&#41; polymorphism in the IL-13 gene&#46; The utility of this polymorphism to predict the GCA prognosis must be confirmed in studies with a higher number of patients&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Investigar si existe asociaci&#243;n del polimorfismo rs20541 &#40;R130Q&#41; del gen de la IL-13 con la susceptibilidad y la expresi&#243;n cl&#237;nica de pacientes con enfermedades inflamatorias cr&#243;nicas asociadas al envejecimiento&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 78 pacientes con arteritis de c&#233;lulas gigantes &#40;ACG&#41;&#44; 174 con polimialgia reum&#225;tica &#40;PMR&#41;&#44; 90 con artritis reumatoide de comienzo en el anciano &#40;EORA&#41;&#44; y 465 controles sanos de la misma zona geogr&#225;fica&#46; El polimorfismo rs20541 &#40;R130Q&#41; para IL-13 se evalu&#243; mediante PCR-RFLP&#46; Los niveles de IL-13 circulante se determinaron por ELISA&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En los pacientes con ACG se observ&#243; una mayor frecuencia del genotipo AA &#91;2&#44;349 &#40;0&#44;994-5&#44;554&#41;&#93;&#44; as&#237; como del alelo A &#91;1&#44;589 &#40;1&#44;085-2&#44;328&#41;&#93; y de portadores de dicho alelo &#91;1&#44;656 &#40;1&#44;021-2&#44;686&#41;&#93; &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; No encontramos diferencias significativas entre los pacientes con PMR y EORA respecto al grupo control&#46; Cuando comparamos las diferentes patolog&#237;as entre s&#237;&#44; tampoco encontramos diferencias significativas entre ellas&#46; En los pacientes con ACG las diferencias en el genotipo se asociaron con el pron&#243;stico de la enfermedad&#46; En pacientes con PMR&#44; el genotipo AA se asoci&#243; con niveles m&#225;s elevados de IL-13 circulante comparado con el GA&#46; Sin embargo&#44; esta asociaci&#243;n no se apreci&#243; para los controles o las otras enfermedades&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La ACG es m&#225;s frecuente en individuos portadores del polimorfismo rs20541 &#40;R130Q&#41; del gen de la IL13&#46; La utilidad de este gen para predecir el pron&#243;stico en ACG debe ser confirmada en estudios con mayor n&#250;mero de pacientes&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; &#193;lvarez-Rodr&#237;guez L&#44; et al&#46; An&#225;lisis del polimorfismo rs20541 &#40;R130Q&#41; del gen de la IL-13 en pacientes con enfermedades inflamatorias cr&#243;nicas asociadas al envejecimiento&#46; Reumatol Clin&#46; 2012&#59;8&#58;321&#8211;7&#46;</p>"
      ]
    ]
    "multimedia" => array:12 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1472
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            "Tamanyo" => 86945
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Serum concentration of IL-13 in patients with giant cell arteritis &#40;GCA&#41;&#44; polymyalgia rheumatic &#40;PRM&#41; and elderly onset rheumatoid arthritis &#40;EORA&#41; in comparison to healthy controls &#40;HC&#41; paired for age and gender&#46; Results are expressed as boxplots with a median and interquartile range for each group&#46; Data was obtained in the active phase of the disease &#40;pre&#41; and in remission after steroid treatment &#40;post&#41;&#46; The number of subjects in each group and the statistical significance when <span class="elsevierStyleItalic">P</span> was under &#46;05 is shown&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Serum concentration of IL-13 in relation to SNP R130Q of the IL-13 gene&#46; Data is presented separately for patients with active giant cell arteritis &#40;GCA&#59; No&#46;&#61;15&#41;&#44; polymyalgia rheumatica &#40;PMR&#59; No&#46;&#61;71&#41; and elderly onset rheumatoid arthritis &#40;EORA&#59; No&#46;&#61;28&#41; and healthy controls paired by age and gender &#40;HC&#59; No&#46;&#61;21&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 2057
            "Ancho" => 2961
            "Tamanyo" => 258109
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Duration in months of steroid treatment &#40;CS&#44; left&#41;&#44; cumulative steroid dose &#40;in middle&#41; and number of relapses &#40;right&#41; in relation to the SNP R130Q of the IL-13 gene&#46; Data is presented separately for active giant cell arteritis &#40;GCA&#44; n&#61;55&#59; superior panel&#41; and polymyalgia rheumatica &#40;PMR&#44; n&#61;120&#59; inferior panel&#41;&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1409
            "Ancho" => 1409
            "Tamanyo" => 42305
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Serum IL-13 concentrations in relation to the SNP R130Q of the IL-13 gene&#46; Data is presented jointly for patients with active disease in any of the 3 cases &#40;No&#46; total&#61;114&#58; giant cell arteritis &#91;GCA&#59; No&#46;&#61;15&#93;&#44; polymyalgia rheumatica &#91;PMR&#59; No&#46;&#61;71&#93; and elderly onset rheumatoid arthritis &#91;EORA&#59; No&#46;&#61;28&#93;&#41;&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">SD&#58; standard deviation&#59; CRP&#58; C reactive protein&#59; ESR&#58; erythrosedimentation rate&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">GCA &#40;n&#61;78&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">PMR &#40;n&#61;174&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">EORA &#40;n&#61;90&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Women&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age at diagnosis &#40;mean&#177;SD&#44; years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#46;7&#177;7&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;9&#177;7&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#46;4&#177;7&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive biopsy&#47;total number of temporal artery biopsies performed&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#47;75 &#40;82&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;64 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;2 &#40;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ischemic manifestations&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VESRSG &#40;mean&#177;SD&#44; mm&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#46;4&#177;32&#46;9<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#46;6&#177;30&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#46;8&#177;34&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CRP &#40;mean&#177;SD&#44; mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;7&#177;5&#46;6<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;7&#177;5&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;3&#177;5&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Follow up time &#40;mean&#177;SD&#44; months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#46;6&#177;47&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#46;8&#177;45&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;1&#177;69&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab212481.png"
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            0 => array:3 [
              "identificador" => "tblfn0005"
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              "nota" => "<p class="elsevierStyleNotepara">GCA vs PMR&#58; <span class="elsevierStyleItalic">P</span>&#8804;&#46;001 both for ESR and CRP&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara">GCA vs EORA&#58; <span class="elsevierStyleItalic">P</span>&#61;&#46;004 for ESR and <span class="elsevierStyleItalic">P</span>&#61;&#46;021 for CRP&#46;</p>"
            ]
          ]
        ]
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Demographic&#44; Clinical and Laboratory Characteristics of Patients With Giant Cell Arteritis &#40;GCA&#41;&#44; Polymyalgia Rheumatica &#40;PMR&#41; and Elderly Onset Rheumatoid Arthritis &#40;EORA&#41; Included in the Study&#46;</p>"
        ]
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ACG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">n&#61;465&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">n&#61;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">IL-13 &#91;db SNP ID rs20541 &#40;R130Q&#41;&#93;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Genotype frequency</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">301&#47;465 &#40;64&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#47;78 &#40;52&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">139&#47;465 &#40;29&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#47;78 &#40;37&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#46;104&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;532 &#40;0&#46;914&#8211;2&#46;567&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25&#47;465 &#40;5&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">08&#47;78 &#40;10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;046&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;349 &#40;0&#46;994&#8211;5&#46;554&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Allelic frequency</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">741&#47;930 &#40;79&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">111&#47;156 &#40;71&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">189&#47;930 &#40;20&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#47;156 &#40;28&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;589 &#40;1&#46;085&#8211;2&#46;328&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Frequency of allelic carriers</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Allele G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">440&#47;465 &#40;94&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#47;78 &#40;89&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;095&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;497 &#40;0&#46;216&#8211;1&#46;146&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Allele A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">164&#47;465 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#47;78 &#40;47&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;039&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;656 &#40;1&#46;021&#8211;2&#46;686&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Allelic and Genotype Frequencies of the rs20541 &#40;R130Q&#41; Polymorphism of the Il-13 Gene in Patients With Giant Cell Arteritis &#40;GCA&#41; Compared to Healthy Controls&#46;</p>"
        ]
      ]
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Genotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PMR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">OR &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">n&#61;465&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">n&#61;174&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">IL-13 &#91;db SNP ID rs20541 &#40;R130Q&#41;&#93;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GG&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">301&#47;465 &#40;64&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">139&#47;465 &#40;29&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#47;174 &#40;29&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;052 &#40;0&#46;714&#8211;1&#46;550&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25&#47;465 &#40;5&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">741&#47;930 &#40;79&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">266&#47;348 &#40;76&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">189&#47;930 &#40;20&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82&#47;348 &#40;23&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#46;207&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;209 &#40;0&#46;900&#8211;1&#46;623&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Frequency of allelic carriers</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Allele G&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">440&#47;465 &#40;94&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">159&#47;174 &#40;91&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;132&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;602 &#40;0&#46;310&#8211;1&#46;171&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Allele A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">164&#47;465 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#47;174 &#40;38&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;448&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;149 &#40;0&#46;802&#8211;1&#46;647&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">n&#61;465&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">n&#61;90&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">IL-13 &#91;db SNP ID rs20541 &#40;R130Q&#41;&#93;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Genotype frequency</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">301&#47;465 &#40;64&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">50&#47;90 &#40;55&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reference&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">139&#47;465 &#40;29&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#47;90 &#40;40&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AA&nbsp;\t\t\t\t\t\t\n
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        "identificador" => "xack38133"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0150" class="elsevierStylePara elsevierViewall">We are especially grateful to I&#241;aki Beares and Marta Gonz&#225;lez &#40;financed by the <span class="elsevierStyleGrantSponsor">Fundaci&#243;n Marqu&#233;s de Valdecilla-IFIMAV</span>&#41; and Carolina Santa Cruz &#40;financed through a research grant from <span class="elsevierStyleGrantSponsor">Schering-Ploug&#44; Spain</span>&#41; for their technical advice&#46; We would also like to thank all of the physicians from the Rheumatology Department who have monitored patients and thank both patients and controls for their participation in the study&#46;</p>"
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2012.07.003

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Year/Month	Html	Pdf	Total

2024 November	17	15	32
2024 October	86	36	122
2024 September	77	29	106
2024 August	59	30	89
2024 July	70	35	105
2024 June	59	31	90
2024 May	83	42	125
2024 April	79	30	109
2024 March	65	38	103
2024 February	91	29	120
2024 January	43	30	73
2023 December	45	45	90
2023 November	42	49	91
2023 October	44	38	82
2023 September	131	33	164
2023 August	44	12	56
2023 July	58	29	87
2023 June	50	30	80
2023 May	61	17	78
2023 April	51	7	58
2023 March	102	34	136
2023 February	68	31	99
2023 January	35	21	56
2022 December	88	46	134
2022 November	78	22	100
2022 October	50	29	79
2022 September	53	40	93
2022 August	78	39	117
2022 July	83	42	125
2022 June	65	44	109
2022 May	73	55	128
2022 April	54	77	131
2022 March	69	63	132
2022 February	43	29	72
2022 January	55	42	97
2021 December	48	41	89
2021 November	72	58	130
2021 October	98	53	151
2021 September	56	45	101
2021 August	36	50	86
2021 July	32	30	62
2021 June	36	38	74
2021 May	79	43	122
2021 April	107	54	161
2021 March	47	37	84
2021 February	32	21	53
2021 January	29	21	50
2020 December	27	21	48
2020 November	33	19	52
2020 October	29	16	45
2020 September	35	24	59
2020 August	29	11	40
2020 July	38	21	59
2020 June	40	10	50
2020 May	36	16	52
2020 April	35	19	54
2020 March	19	6	25
2019 April	1	2	3
2019 January	1	0	1
2018 December	0	1	1
2018 May	3	0	3
2018 April	152	4	156
2018 March	45	7	52
2018 February	49	3	52
2018 January	39	2	41
2017 December	57	7	64
2017 November	46	4	50
2017 October	59	6	65
2017 September	38	5	43
2017 August	63	4	67
2017 July	51	7	58
2017 June	102	12	114
2017 May	98	9	107
2017 April	76	5	81
2017 March	80	12	92
2017 February	65	6	71
2017 January	56	4	60
2016 December	99	12	111
2016 November	86	4	90
2016 October	122	7	129
2016 September	116	4	120
2016 August	113	5	118
2016 July	49	16	65
2016 January	1	0	1
2015 December	3	17	20
2015 October	1	17	18
2015 September	1	0	1
2015 August	2	0	2
2015 July	18	6	24
2015 June	48	6	54
2015 May	40	14	54
2015 April	45	13	58
2015 March	55	5	60
2015 February	64	8	72
2015 January	68	5	73
2014 December	53	11	64
2014 November	30	9	39
2014 October	35	6	41
2014 September	30	6	36
2014 August	36	11	47
2014 July	38	18	56
2014 June	74	9	83
2014 May	53	14	67
2014 April	47	11	58
2014 March	49	18	67
2014 February	41	25	66
2014 January	54	11	65
2013 December	33	8	41
2013 November	29	13	42
2013 October	51	8	59
2013 September	55	11	66
2013 August	48	8	56
2013 July	42	8	50
2013 June	35	11	46
2013 May	43	15	58
2013 April	52	10	62
2013 March	51	11	62
2013 February	35	11	46
2013 January	56	18	74
2012 December	60	18	78
2012 November	10	1	11

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