rs2239673

This case-control study of 2,322 Korean participants (1,316 RA cases, 1,006 controls) identified multiple SNPs in an IRAK1-MECP2 locus on Xq28 associated with rheumatoid arthritis susceptibility. The most significant association was with rs1734792 (P=0.00089, OR=1.33), while two nonsynonymous IRAK1 SNPs rs1059702 (P=0.0034, OR=1.31) and rs1059703 (P=0.0042, OR=1.31) showed functional effects with a major haplotype conferring 1.7-fold increased RA risk and enhanced IRAK1-mediated NF-κB activity.

This case-control study examined the association of two IRAK1 gene polymorphisms (rs3027898 and rs1059702) with systemic lupus erythematosus (SLE) in a Chinese Han population of 667 SLE patients and 667 healthy controls. The C allele of rs3027898 was significantly associated with increased SLE risk (OR = 1.438, 95% CI = 1.180-1.753, p < 0.001), as was the A allele of rs1059702 (OR = 1.383, 95% CI = 1.143-1.674, p = 0.001). Notably, the C allele of rs3027898 was associated with decreased risk for oral ulcers in SLE patients.

This comprehensive review examines genetic associations in type I interferon-related signaling pathways across multiple autoimmune diseases. The authors review evidence linking dysregulated interferon alpha (IFNα) signaling to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune conditions, identifying multiple susceptibility genes including IFIH1, IRF5, STAT4, TYK2, BLK, BANK1, FCGR2A, and TREX1 with well-replicated associations and functional relevance to IFN pathway dysfunction.