rs2070197

Case-control study in 642 Han Chinese SLE patients and 642 healthy controls examining polymorphisms in IRF5 and TYK2 genes. IRF5 rs2004640 (T allele, OR=1.41, p=0.0003) and protective haplotype DAG (OR=0.71, p=6.2×10⁻⁵) and risk haplotype IAT (OR=1.53, p=0.0005) showed significant association with SLE. TYK2 rs280500 (A allele, OR=1.47, p=8.83×10⁻⁶), rs2304256 (G allele, OR=1.59, p=3.71×10⁻⁶), and rs8108236 (A allele, OR=1.39, p=0.0004) were significantly associated with SLE. A three-way gene-gene interaction between TYK2 rs280500, rs2304256 and IRF5 rs10954213 was found (p<0.0001).

This association study of 664 German Wegener's granulomatosis (WG) patients and 952 controls evaluated 22 SNPs across 13 candidate genes identified from RA and SLE studies. The strongest finding was a protective four-SNP IRF5 haplotype (rs2004640_G/rs60344245_del/rs2070197_T/rs10954213_G) with reduced WG risk (p=0.0000897, OR 0.73, 95% CI 0.62-0.85). SNPs in TNFAIP3 and CDK6 also showed nominally significant associations, suggesting WG shares some genetic risk factors with other autoimmune diseases.

A case-control study of 263 non-anterior uveitis patients and 724 healthy Spanish controls examined three IRF5 SNPs (rs2004640, rs2070197, rs10954213) for association with uveitis and macular edema. Two functional variants, rs2004640 and rs10954213, showed significant protective associations with absence of macular edema (OR=1.48, P_FDR=5.07E-03 and OR=1.54, P_FDR=3.37E-03, respectively), suggesting IRF5 genetic variation influences macular edema development in uveitis patients.

This study examined IRF5 genetic variants in 199 systemic lupus erythematosus (SLE) patients to determine if the IRF5 SLE risk haplotype associates with elevated serum interferon-α (IFN-α) activity. SLE patients with risk/risk or risk/neutral IRF5 genotypes showed significantly higher serum IFN-α activity compared to protective genotypes (P = 0.025), with the most pronounced effect in patients positive for anti-RBP or anti-dsDNA autoantibodies (P = 0.012). The rs3807306 genotype independently associated with high IFN-α levels in the autoantibody-positive subgroup.

This case-control and family-based association study found a strong genetic association between IRF5 polymorphisms and systemic lupus erythematosus (SLE) in Mexican patients. SNP rs2070197 showed the strongest association (P = 1.26 × 10⁻²¹) with an odds ratio of 3.19 for the risk allele, and homozygotes for the risk haplotype had an odds ratio of 10.46. Notably, the risk haplotype was significantly more frequent in healthy Mexican individuals compared to Europeans, and even higher in Mexican Indians, suggesting genetic admixture influences SLE susceptibility.