Elsevier

Genomics

Volume 90, Issue 1, July 2007, Pages 6-13
Genomics

Identification of a two-loci epistatic interaction associated with susceptibility to rheumatoid arthritis through reverse engineering and multifactor dimensionality reduction

https://doi.org/10.1016/j.ygeno.2007.03.011Get rights and content
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Abstract

Altered synovial fibroblast (SF) transcriptional activity is a key factor in the disease progression of rheumatoid arthritis (RA). To determine the transcriptional regulatory network associated with SF response to an RA proinflammatory stimulus we applied a CARRIE reverse engineering approach to microarray gene expression data from SFs treated with RA synovial fluid. The association of the inferred gene network with RA susceptibility was further analyzed by a case–control study of promoter single-nucleotide polymorphisms, and the presence of epistatic interactions was determined using the multifactor dimensionality reduction methodology. Our findings suggest that a specific NF-κB transcriptional regulatory network of 13 genes is associated with SF response to RA proinflammatory stimulus and identify a significant epistatic association of two of its genes, IL6 and IL4I1, with RA susceptibility.

Keywords

Rheumatoid arthritis
Synovial membrane
Fibroblast
DNA microarrays
Bioinformatics
Transcription factor
Promoter
SNPs
Genetic epistasis
Genetic susceptibility

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