rs10954213

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 comprehensive review analyzes microRNA-related single nucleotide polymorphisms (SNPs) in gastric cancer, focusing on the most commonly studied variants including pre-miR-146a rs2910164, pre-miR-196a2 rs11614913, pre-miR-149 rs2292832, and pre-miR-499 rs3746444. The paper reviews 45 studies examining associations between miRNA polymorphisms and gastric cancer risk, including 18 studies on rs2910164 showing conflicting results (OR range 0.81-1.58), 13 studies on rs11614913 with no overall significant association, and analysis of pri-miRNA, pre-miRNA, promoter, and 3'-UTR variants. Additional variants identified include rs712 in let-7 (OR = 3.05; 95% CI = 1.53-6.08), rs12904 in miR-200c (OR = 0.65; 95% CI = 0.50-0.85), and rs12537 in miR-181a (OR = 1.72; 95% CI = 1.36-2.16).

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.

This functional study examined four genetic variants in the IRF5 gene (rs2004640, rs10488631, rs10954213, and a CGGGG indel) in 44 Swedish SLE patients and 16 healthy controls. The risk haplotype (H2) was associated with significantly elevated IRF-5 transcript and protein expression in patient blood cells (p=0.0084 for total IRF-5). rs10488631 showed the only significant independent association with increased transcription from exon 1C (p=0.0155). Minigene assays demonstrated that rs2004640, the CGGGG indel, and type I interferons regulate IRF-5 expression.

A case-control association study of 281 Japanese systemic sclerosis (SSc) patients and 477 healthy controls examined three IRF5 SNPs (rs2004640, rs10954213, rs2280714) previously associated with systemic lupus erythematosus. rs2280714 showed the strongest association with SSc (OR 1.42, P=0.0012 in all SSc; OR 1.70, P=0.00013 in diffuse cutaneous SSc). The rs2004640 association was replicated in the recessive model, particularly in the anti-topoisomerase I antibody-positive subset.

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 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.

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.

This study identified 2,530 genes with alternative polyadenylation quantitative trait loci (apaQTL) in 373 European individuals from the GEUVADIS dataset, discovering ~160,000 genetic variants affecting 3' UTR isoform expression. Notably, rs10954213 in IRF5 was confirmed to affect APA regulation in systemic lupus erythematosus (SLE) patients. apaQTLs showed significant enrichment in GWAS hits, particularly for immune disorders (OR=5.41) and neurological disorders (OR=4.32), suggesting that alternative polyadenylation is an important intermediate molecular phenotype linking genetic variation to complex disease susceptibility.