Analysis of TNFAIP3, IRAK1, and TLR4 Gene Polymorphisms in Patients With Rheumatoid Arthritis

OBJECTIVE: Rheumatoid arthritis (RA) arises from a complex interplay of polygenic susceptibility, epigenetic factors, and environmental modifiers. This study investigated the correlation between RA and Tumor necrosis factor α-induced protein 3 (TNFAIP3), Interleukin-1 receptor-associated kinase 1 (IRAK1), and Toll-like receptor 4 (TLR4) gene polymorphisms. METHODS: A sample of 308 RA cases and 310 matched controls was included. Genotyping of the TNFAIP3, IRAK1, and TLR4 was performed via mass spectrometry. RESULTS: Compared to healthy controls, individuals carrying the rs1059703 A allele (odds ratio (OR) = 0.640, 95% confidence interval (CI): 0.458-0.895, p = 0.009) of IRAK1, individuals carrying the rs5029930 C allele (OR = 0.469, 95% CI: 0.298-0.739, p = 0.001), and AC genotype (OR = 0.427, 95% CI: 0.255-0.716, p = 0.001) of TNFAIP3 had a lower RA risk. Individuals carrying the rs5029939 C allele (OR = 2.401, 95% CI: 1.436-4.017, p = 0.001) of TNFAIP3, individuals carrying the rs7873784 C allele (OR = 1.549, 95% CI: 1.101-2.179, p = 0.012), and CG genotype (OR = 1.489, 95% CI: 1.011-2.193, p = 0.043) of TLR4 had a higher RA risk. CONCLUSION: In summary, the TNFAIP3, IRAK1, and TLR4 gene polymorphisms are associated with RA susceptibility.