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Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. To date, many studies explored the associations between tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs6920220, rs2230926, and rs5029937 polymorphisms and the risk of rheumatoid arthritis (RA), but with contradictory results. We therefore conducted a comprehensive meta-analysis to address the associations. We searched in the databases of PubMed and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Stata 11.0 software. A total of 21 case-control studies for these three single nucleotide polymorphisms (SNPs) were included in this meta-analysis. Meta-analysis indicated that TNFAIP3 gene rs6920220, rs2230926, and rs5029937 polymorphisms were associated with the increased risk of RA. Stratification analysis of ethnicity found that rs6920220 and rs5029937 polymorphisms increased the risk of RA among Caucasians, while rs2230926 polymorphism increased the risk of RA among Asians. In summary, this meta-analysis confirms that TNFAIP3 gene polymorphisms may play important roles in the pathogenesis of RA.

SUBMITTER: Shen N

PROVIDER: S-EPMC5400544 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arthritis.

Shen Nan N Ruan Yuan Y Lu Yajun Y Jiang Xuefeng X Sun Huiqing H Gao Gongming G Nong Luming L Ren Kewei K

Oncotarget 20170301 13

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. To date, many studies explored the associations between tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs6920220, rs2230926, and rs5029937 polymorphisms and the risk of rheumatoid arthritis (RA), but with contradictory results. We therefore conducted a comprehensive meta-analysis to address the associations. We searched in the databases of PubMed and Em ...[more]

PMID: 28199970

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Project description: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.

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Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arthritis.

Publications

Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arthritis.

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