rs1059702

Genome-wide association study in 1,174 Korean SLE cases and 4,248 controls identified 12 genome-wide significant loci, including a novel locus spanning ATG16L2, FCHSD2, and P2RY2 peaking at rs11235667 (P=1.0×10⁻⁸, OR=0.59). The study replicated 10 previously established SLE risk loci (STAT4, TNFSF4, TNFAIP3, IKZF1, HIP1, IRF5, BLK, WDFY4, ETS1, IRAK1-MECP2) and identified novel independent effects in TNFAIP3 and TNFSF4. HLA-DRB1*1501 and HLA-DQB1*0602 were the strongest HLA associations (P=5.55×10⁻¹⁶, OR=1.85 and OR=1.90 respectively).

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.