Objectives: Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, which regulate the production of pro-inflammatory cytokines. Polymorphisms in the IRF5 gene have been associated with susceptibility to systemic lupus erythematosus (SLE) in Caucasian and Asian populations, but their involvement in other autoimmune diseases is still uncertain. Here, we assessed the genetic role of IRF5 in susceptibility to rheumatoid arthritis (RA) in the Japanese subjects.
Methods: We selected thirteen single nucleotide polymorphisms (SNPs) and a CGGGG insertion-deletion polymorphism in the IRF5 gene. We performed two sets of case-control comparisons using Japanese subjects (first set: 830 RA patients and 658 controls; second set: 1,112 RA patients and 940 controls), and then performed a stratified analysis by the HLA-DRB1 shared epitope (SE) status. We genotyped the SNPs using TaqMan assays.
Results: A significant association of the rs729302 A allele with RA susceptibility was found in both sets (OR=1.22 [95%CI 1.09-1.35], P=0.00032 in the combined analysis). When the patients were stratified by the SE, the rs729302 A allele was found to confer increased risk to RA in SE-negative patients (OR=1.50 [95%CI 1.17-1.92], P=0.0013) as compared with patients carrying the SE (OR=1.11 [95%CI 0.93-1.33], P=0.24). No genotyped polymorphisms but rs729302 were significantly associated with RA susceptibility in both sets.
Conclusion: These findings indicate that the promoter polymorphism of IRF5 is a genetic factor conferring predisposition to RA, and that it contributes considerably to disease pathogenesis in SE-negative patients.