Polymorphisms in the CTLA-4 Gene and Rheumatoid Arthritis Susceptibility: A Meta-analysis

Introduction The +49A/G polymorphism and CT60 polymorphism in the CTLA-4 gene have been extensively examined for the association with rheumatoid arthritis (RA); however, results of different studies have been inconclusive. The aim of this study is to comprehensively evaluate the genetic risks of +49A/G and CT60 polymorphisms in the CTLA-4 gene for RA. Methods A meta-analysis was carried out to analyze the association of +49A/G and CT60 polymorphisms with RA risk. Results A total of 30 case-control studies in 20 articles were included in this meta-analysis. The results indicated that the variant G allele carriers (GG + GA) of +49A/G polymorphism had an 18% increased risk of RA when compared with the homozygote AA (odds ratio (OR)=1.18, 95% confidence interval (CI): 1.04-1.34 for GG + AG vs. AA). In addition, the variant CT60 A allele carriers of CT60 polymorphism had a 14% decreased risk of RA when compared with the homozygote GG (OR=0.86, 95% CI=0.78-0.95 for AA + AG vs. GG). In the subgroup analysis by ethnicity, significant elevated RA risks were associated with +49G allele carriers in Asians, but not in Europeans. However, for CT60 polymorphism, significant decreased RA risks were associated with CT60 A allele carriers in Europeans, but not in Asians. Conclusions This meta-analysis suggested that the +49A/G and CT60 polymorphisms in the CTLA-4 gene may be risk factors for RA.