Abstract

BackgroundRheumatoid 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.MethodsA case–control study of 1280 RA patients and 1280 matched healthy controls was conducted.ResultsThis 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).ConclusionsRs10499194 and rs2230926 polymorphisms in the TNFAIP3 gene region may be susceptibility factors for rheumatoid arthritis in the northern Chinese Han population.

Highlights

  • Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints

  • To identify the role of the polymorphisms in the TNFAIP3 gene on the risk of RA in Asian population, in the present study, we describe a case–control study of 1280 RA cases and 1280 controls from northern Chinese han population; stratified analyses were carried on by gender and age; we explored the interaction between genetic polymorphisms in the development of RA

  • The results showed that the increased risks were significant among the rs2230926 variant genotypes (TG) and rs10499194 variant genotypes (CT) and the corresponding odds ratios (OR) were 1.42 and 1.52, respectively

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Summary

Introduction

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. 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. Rheumatoid arthritis (RA) is a systemic autoimmune disease It is characterized by chronic destructive inflammation in synovial joints. The key role of nuclear factor-κB (NF-κB)dependent gene expression in the development of autoimmune diseases including RA is generally accepted. The development of severe inflammation of the joints are found in A20-deficient mice [6]. A20 deficiency in myeloid cells spontaneously develops a severe destructive polyarthritis with many features of RA in mice [7]. DCs need A20 to preserve immune quiescence and prevents colitis and spondyloarthritis in mice [10]

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