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Vol. 17. Issue 8.
Pages 447-455 (October 2021)
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Vol. 17. Issue 8.
Pages 447-455 (October 2021)
Original Article
DOI: 10.1016/j.reumae.2020.03.003
The association between interleukin-6 promoter polymorphisms and rheumatoid arthritis by ethnicity: A meta-analysis of 33 studies
Asociación entre los polimorfismos del promotor de la interleucina-6 y la artritis reumatoide analizado por etnicidad: un metaanálisis de 33 estudios
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Blanca T. Pacheco-Sotoa,1, Leonardo M. Porchiab,1, William C. Lara-Vazqueza, Enrique Torres-Rasgadoa, Ricardo Perez-Fuentesa,b, M. Elba Gonzalez-Mejiaa,
Corresponding author
elba.gonzalezmejia@gmail.com

Corresponding author.
a Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, 13 Sur 2901 Col. Volcanes, C.P. 72420 Puebla, Pue, Mexico
b Laboratorio de Investigación en Fisiopatologia de Enfermedades Crónicas, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Delegación Puebla, Km 4.5 Carretera Federal Atlixco-Metepec, C.P. 42730 Atlixco, Puebla, Mexico
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Tables (4)
Table 1. Characteristics of included studies.
Table 2. The association between IL-6 promoter polymorphism and the risk of developing Rheumatoid Arthritis.
Table 3. The association of the −174 G>C polymorphism on the development of Rheumatoid Arthritis, stratified by ethnicity.
Table 4. The association of the −572 G>C polymorphism on the development of Rheumatoid Arthritis, stratified by ethnicity.
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Abstract
Objective

We performed a meta-analysis to determine the effect Interleukin-6 (IL-6) promoter polymorphism (−174 G>C, −572 G>C, and −597 G>A) have on the development rheumatoid arthritis (RA) by ethnicity.

Material and methods

PubMed, EBSCO, LILACS, and Scopus databases were searched for studies exploring the association between any IL6 polymorphisms and RA until November 2018. Genotype distributions were extracted and, depending on the level heterogeneity, determined by the ψ2-based Q test and the Inconsistency Index (I2), fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models.

Results

From 708 identified publications, 33 were used in this analysis. For the −174 polymorphism, Asians (ORheterozygous=7.57, 95%CI: 2.28–25.14, ORhomozygous=5.84, 95%CI: 2.06–16.56, ORdominant=7.21, 95%CI: 2.30–22.63, ORrecessive=5.04, 95%CI: 1.78–14.28, ORallelic=6.60, 95%CI: 2.26–19.28, p<.05) and Middle East countries (ORheterozygous=2.30, 95%CI: 1.10–4.81, ORdominant=2.27, 95%CI: 1.22–4.22, ORallelic=2.29, 95%CI: 1.24–4.23, p<.05) were associated with a significant risk of developing RA. Whereas, for Latinos, the C-allele was associated with a benefit (ORhomozygous=0.26, 95%CI: .08–.82, ORrecessive=.25, 95%CI: .08–.80, p<.05). For the −572 polymorphism, Asians demonstrated a significant association for the homozygous and recessive genetic models (8 studies, ORhomozygous=1.56, 95%CI: 1.16–2.09, ORrecessive=1.63, 95%CI: 1.08–2.45, p<.05). For the −597 polymorphism, no association was observed.

Conclusions

Here, the −174 G>C polymorphism increased the risk of developing RA in Asians and Middle East populations. Interestingly, for Latinos, the polymorphism was associated with a benefit. For the −572 polymorphism, only the Asian population showed an increased risk of developing RA for the CC genotype.

Keywords:
Interleukin-6
Rheumatoid arthritis
Single nucleotide polymorphism
Meta-analysis
Ethnicity
Resumen
Objetivos

Realizamos un meta-análisis para determinar el efecto de los polimorfismos del promotor de interleucina-6 (IL-6) (-174 G>C, -572 G>C, y -597 G>A) sobre el desarrollo de artritis reumatoide (RA) analizado por etnicidad.

Materiales y métodos

En las bases de datos PubMed, EBSCO, LILACS y Scopus se buscaron estudios con la asociación entre polimorfismo de IL-6 y RA publicados hasta noviembre 2018. se obtuvieron las distribuciones de genotipo y de acuerdo al nivel de heterogeneidad el efecto fijo o aleatorio fueron utilizados para calcular los Odds Ratio (OR) con intervalos de confianza del 95% para los modelos genéticos heterocigoto, homocigoto, dominante, recesivo y alélico.

Resultados

De 708 estudios identificados, 33 fueron utilizados para este análisis. Para el polimorfismo -174, los países Asiáticos (ORheterocigoto=7,57, 95%CI: 2,28–25,14, ORhomocigoto=5,84, 95%CI: 2,06-16,56, ORdominante=7,21, 95%CI: 2,30-22,63, ORrecesivo=5,04, 95%CI: 1,78-14,28, ORalélico=6,60, 95%CI: 2,26-19,28, p<0,05) y del Medio Oriente (ORheterocigoto=2,30, 95%CI: 1,10-4,81, ORdominante=2,27, 95%CI: 1,22-4,22, ORalélico=2,29, 95%CI: 1,24-4,23, p<0,05) están asociados con el riesgo de desarrollar RA significativamente. Mientras que, para los Latinos, el alelo-C está asociado con un beneficio (ORhomocigoto=0,26, 95%CI: 0,08-0,82, ORrecesivo=0,25, 95%CI: 0,08-0,80, p<0,05). Para el polimorfismo -572, los Asiáticos están asociados significativamente con los modelos genéticos homocigoto y recesivo (8 estudios, ORhomocigoto=1,56, 95%CI: 1,16-2,09, ORrecesivo=1,63, 95%CI: 1,08-2,45, p<0,05). Para el polimorfismo -597, no se observó asociación.

Conclusiones

El polimorfismo -174 G>C aumenta el riesgo de desarrollar RA en población Asiática y Medio Oriente. Curiosamente, para los Latinos el polimorfismo está asociado con un beneficio. Para el polimorfismo -572, solo la población Asiática demuestra una aumento en el riesgo de desarrollar RA con el genotipo CC.

Palabras clave:
Interleucina-6
Artritis reumatoide
Polimorfismo de un solo nucleótido
Metaanálisis
Etnicidad

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