rs1990760

A case-control study of 180 Chinese children (60 healthy controls, 60 mild EV71-HFMD, 60 severe EV71-HFMD) examined DNA methylation and SNPs in DDX58 and IFIH1 genes as biomarkers for hand, foot and mouth disease severity. DDX58 rs3739674 GG genotype was significantly associated with severe EV71-HFMD (OR 1.421, p=0.013), with lower DDX58 mRNA expression and higher promoter methylation in severe patients.

This candidate gene study of 130 Danish children with type 1 diabetes examined associations between 20 diabetes-related SNPs and diabetic retinopathy progression over 16 years. The CTSH/rs3825932 variant was associated with reduced risk of progression to proliferative diabetic retinopathy (OR=0.20, p=2.4×10⁻³, p_adjust=0.048), while ERBB3/rs2292239 was associated with increased risk of two-step DR progression (OR=2.76, p=7.5×10⁻³, p_adjust=0.15). The CTSH association remained significant after multiple testing correction.

This study confirms the association between the IFIH1 Ala946Thr polymorphism (rs1990760) and type 1 diabetes in Hungarian (OR 1.29, p=0.002) and Finnish populations (OR 1.14, p=0.232). A meta-analysis of 9,546 cases and 11,000 controls across six European populations showed a significant overall association (OR 1.176, p=5.3×10⁻¹⁵) with evidence for heterogeneity in effect sizes across populations, suggesting environmental factors may modulate genetic risk.

This case-control study of 591 late-onset Finnish type 1 diabetes patients (ages 15-40) and 1,538 controls identified SNPs at the INS (rs689, OR=0.57, p=2.77×10⁻⁹), PTPN22 (rs2476601, OR=1.50, p=3.98×10⁻⁶), and IFIH1 (rs1990760, OR=0.81, p=0.0028) loci significantly associated with disease. Notably, IL2RA SNPs (rs11594656 and rs41295061) showed no disease association but had independent effects on age at diagnosis (HR=0.83 and 0.74, p=0.015 and 0.006 respectively), making IL2RA a major determinant of disease onset timing.

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 validates the association between IFIH1 gene variants and type 1 diabetes in an independent cohort of 589 family trios (1,767 individuals) of mixed European descent. Using family-based association testing, the authors confirmed significant associations for rs2111485 (OR=0.84, p=0.0244) and rs984971 (OR=0.85, p=0.0455), replicating the previously reported IFIH1 locus findings. The results support the role of innate antivirus immunity in type 1 diabetes pathogenesis.