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Background  Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. It is well known that genetic and environmental risk factors and their interaction contribute to RA pathogenesis. This study aimed to investigate the association between the critical polymorphisms in the  tumor necrosis factor α (TNFα)-induced protein 3(TNFAIP3)  gene and the risk of RA in a large northern Chinese Han population.    Methods  A case–control study of 1280 RA patients and 1280 matched healthy controls was conducted.    Results  This study showed that carriers of the rs2230926 TG genotype or rs10499194 CT genotype had an increased risk for RA compared with those carrying the wild genotype (rs2230926: OR = 1.48, 95% CI = 1.17-1.86,  p  = 0.001; rs10499194: OR = 2.00, 95% CI = 1.46-2.74,  p  < 0.001). The combined rs2230926TG/GG or rs10499194 CT/TT were associated with an increased risk of RA (ORs were 1.50 and 2.01, 95% CIs were 1.19-1.88 and 1.47-2.74, respectively, both  p  < 0.001). There was not significant association between rs13207033 polymorphism and RA risk. Subset analysis stratified to gender showed that the increased risks were significant among the genotypes TG, TG/GG of rs2230926 and CT, CT/TT of rs10499194 and the corresponding ORs were 1.42 (95%  CI = 1.10-1.83,  p  = 0.006), 1.44(95% CI = 1.12-1.85,  p  = 0.004), 1.52(95% CI = 1.05-2.20,  p  = 0.026) and 1.52(95% CI = 1.06-2.19,  p  = 0.023) in the female population. Stratified analyses by age found that rs2230926(TG, TG/GG) and rs10499194(CT, CT/TT) polymorphisms were associated with RA risks in population ≤53 years old and among >53 years old only rs10499194(CT, TT, CT/TT) polymorphism had significant results. The interaction analysis suggested that individuals with both risk genotypes of the two SNPs have a higher elevated risk of RA than those with only one of them (ORs were 3.44 compared to 1.74 and 1.35). The haplotype results showed that individuals with the rs2230926G-rs13207033G-rs10499194C haplotype were associated with increased risks of RA (OR = 1.37, 95% CI = 1.08-1.74,  p  = 0.010).    Conclusions  Rs10499194 and rs2230926 polymorphisms in the  TNFAIP3  gene region may be susceptibility factors for rheumatoid arthritis in the northern Chinese Han population.

Single nucleotide polymorphisms in TNFAIP3 were associated with the risks of rheumatoid arthritis in northern Chinese Han population