rs4251961

A case-control study of 279 cirrhotic patients (178 with acute-on-chronic liver failure, 101 controls) examining IL-1 gene cluster polymorphisms found that IL-1β rs1143623 CC genotype (OR=0.34) and IL-1ra rs4251961 TC genotype (OR=0.58) were protective against ACLF and associated with lower inflammatory cytokine levels and reduced 28-day mortality. The protective genotypes modulated systemic inflammation through altered IL-1 signaling pathways.

This genome-wide association study (GWAS) identified genetic variants influencing interleukin levels in African Americans. IL-10 levels showed genome-wide significant associations with 8 SNPs, most notably rs5743185 in PMS1 (p=2.30×10⁻¹⁰), with successful replication of rs17365948 in YWHAZ. IL-1Ra levels showed suggestive associations with SNPs in ASB3 and the IL-1 gene family, with replication of rs4251961. IL-6 levels showed genome-wide significant association with one variant near RP11-314E23.1 (p=8.63×10⁻⁹).

A case-control study of 326 cases and 748 controls identified 25 SNPs in genes involved in platelet activation, angiogenesis, and inflammatory response that modify the risk of aspirin-related upper gastrointestinal hemorrhage (UGIH). Seven SNPs (rs1387180, rs2238631, rs1799964, rs5050, rs689466, rs1799983, rs7756935) were positive modifiers increasing UGIH risk in aspirin users (RERI 1.75-4.95), while nine SNPs (rs2243086, rs1131882, rs4311994, rs10120688, rs4251961, rs3778355, rs1330344, rs5275, rs3779647) were negative modifiers reducing risk (RERI -2.74 to -0.95). Aspirin exposure alone increased UGIH risk approximately 5.82-fold (95% CI: 2.2-10.08).

A meta-analysis of 4,107 type 2 diabetes cases and 5,187 controls from three GWA studies found no evidence that common variants altering circulating inflammatory protein levels (IL-18, IL-6R, CRP, IL1RN, PAI1, MIF) or variants predisposing to autoimmune diseases (type 1 diabetes, rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, SLE) are associated with type 2 diabetes risk. For example, rs2250417 in IL18 showed OR=1.00 (95% CI 0.99-1.03) versus the expected OR of ~1.15 if inflammation were causal, suggesting inflammatory markers are likely secondary rather than causative in type 2 diabetes.

This computational modeling study examined IL-1 protein-receptor interactions in schizophrenia by analyzing genetic polymorphisms associated with the disease. The authors identified and analyzed 12 SNPs in IL-1 pathway genes (IL-1α, IL-1β, IL-1RA) and modeled their structural effects. The key finding was that rs315952 (p.Ser130Arg in IL-1RA) leads to weakened binding of IL-1RA to IL-1 receptors, potentially triggering the IL-1 signaling pathway and contributing to schizophrenia pathogenesis through dysregulated immune response.