Association Between CTLA-4 Gene Polymorphism and Risk of Rheumatoid Arthritis (RA): Evidence from a Meta-analysis Involving 21681 Cases and 23457 Controls.

Abstract Background: Genetic predisposition was well known to be involved in the pathogenesis of Rheumatoid arthritis (RA). Lots of genetic studies on association between Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) polymorphisms and RA susceptibility had been accumulated in the past few decades, yet reporting inconsistent results. Therefore, we summarized the most-often 3 polymorphisms and performed a meta-analysis to comprehensively evaluate the effect of CTLA-4 gene polymorphisms on RA risk.Methods: Five electronic databases were searched for eligible studies till Oct. 2020. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association. Stratified analysis was conducted by ethnicity.Results: In total, 42 case-control studies including 21681 cases and 23457 controls were obtained. For rs3087243 polymorphism, significant association was detected in Asians (A vs. G: OR=0.77, 95%CI=0.65-0.90, P=0.001; AA vs. GG: OR=0.67, 95%CI=0.48-0.94, P=0.02) and Caucasians (A vs. G: OR=0.89, 95%CI=0.86-0.93, P<0.00001; AA vs. GG: OR=0.81, 95%CI=0.75-0.88, P<0.00001). For rs231775 polymorphism, significant association was observed in the overall (G vs. A: OR =1.16, 95%CI=1.08-1.25, P<0.0001; GG vs. AA: OR=1.29, 95%CI=1.12-1.50, P=0.0006), in Asians (G vs. A: OR=1.27, 95%CI=1.10-1.47, P=0.001; GG vs. AA: OR=1.58, 95%CI=1.24-2.01, P=0.0002), and not in Caucasians. However, there was no association between rs5742909 polymorphism and RA risk.Conclusion: This meta-analysis confirmed that rs3087243 and rs231775 polymorphism were associated with the risk of RA in both overall population and ethnic-specific analysis, but there was no association between rs5742909 polymorphism and RA risk.