rs1800610

Population-based case-control study of 876 cervical cancer cases, 517 vulvar cancer cases, and 1,100 controls examining genetic variation in TLR and NFκB pathways. The TNF region was significantly associated with cervical cancer (gene-based P=2.0×10⁻⁴) and vulvar cancer (gene-based P=1.0×10⁻⁴) risk. The rare A allele of rs2239704 in the LTA gene 5' UTR was significantly associated with increased cervical cancer risk (OR=1.31, 95% CI: 1.15–1.50) and vulvar cancer risk (OR=1.51, 95% CI: 1.30–1.75).

This case-control association study examined six TNF-LTA locus variants in 2,115 North Indian subjects (1,073 type 2 diabetes patients, 1,042 controls). The TNF promoter variant rs1800630 and LTA non-synonymous variant rs2229094 showed obesity-dependent protection from type 2 diabetes (OR=0.83, P=0.005 and OR=0.86, P=0.02, respectively). The haplotype carrying all major alleles conferred susceptibility, with stronger effects in non-obese subjects (OR=1.45, P=2×10⁻⁴). The minor alleles were associated with lower BMI, waist circumference, and hsCRP.

This cross-sectional study of 627 unvaccinated COVID-19 patients examined associations between cytokine gene polymorphisms and COVID-19 severity. Five polymorphisms were significantly associated with severe disease: TNF-α rs1800610 A allele (OR=1.50), IL-6 rs1800796 C allele (OR=1.64), IL-10 rs1800871 T allele (OR=1.94), IL-10 rs1800872 A allele (OR=1.87), and CCL5 rs3817656 G allele (OR=1.64). IL-10 rs1800629 was protective against moderate and severe disease.

A large population-based case-control study of TNF-LTA genetic variation in 5,546 breast cancer cases and 5,219 controls (USA and Poland cohorts) found that the variant A allele of rs361525 in the TNF promoter region was associated with modestly increased breast cancer risk (per allele OR=1.18, 95% CI 1.04-1.35, p=0.008). Eight TNF and LTA SNPs were genotyped; haplotype analyses showed the GAG haplotype carrying rs361525 A was associated with elevated risk, while the well-studied TNF-308 variant (rs1800629) showed no association.

This review examines slowly progressive type 1 diabetes mellitus (SPIDDM), also known as latent autoimmune diabetes in adults (LADA), discussing its pathogenesis, diagnostic markers, and genetic associations. Key findings include T-cell-mediated insulitis and pseudoatrophic islets characteristic of type 1 diabetes, absence of amyloid deposition seen in type 2 diabetes, and identification of multiple genetic susceptibility loci including HLA haplotypes, PTPN22 rs2476601, INS rs689, CTLA4, TCF7L2 rs7903146, ZMIZ1 rs12571751, SH2B3 rs7310615, and PFKFB3 rs1983890. GAD autoantibodies and HLA genotypes are important risk factors for beta-cell failure progression.