Abstract
Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) gene polymorphisms may be involved in the risk of Rheumatoid arthritis (RA). However, evidence for the association remains controversial. Therefore, we performed a meta-analysis to confirm the relationship between CTLA-4 gene polymorphisms and RA. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association. Stratified analysis was conducted by ethnicity. In total, 66 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), and 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), but not in Caucasians. However, there was no association between rs5742909 polymorphism and RA. 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.
Highlights
Rheumatoid arthritis, one of the most common inflammatory joint diseases in humans, is characterized by inflammation in synovium, destruction of cartilage and bone, generation of autoantibody, and complications of systemic organs [1]
This was the first meta-analysis to investigate the association between the three most-often single nucleotide polymorphisms (SNPs) of Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and Rheumatoid arthritis (RA) susceptibility
From the data integration of 66 studies in 21681 cases and 23457 controls, we found that the rs3087243 SNP decreased the risk of RA risk in Caucasians and Asians, the rs231775 SNP of CTLA-4 increased RA risk in Asians but not in Caucasians and Africans, and the rs5742909 SNP was not significantly associated with RA risk in both Caucasians and Africans
Summary
Rheumatoid arthritis, one of the most common inflammatory joint diseases in humans, is characterized by inflammation in synovium, destruction of cartilage and bone, generation of autoantibody, and complications of systemic organs [1]. Because of the results of reduced physical function, declined work capacity, decreased quality of life, and increased comorbid risk, RA carries heavy socioeconomic burden [3]. In twin studies 50–65% of the risk for developing RA is ascribed to its heritability [4], indicating genetic factors have a strong effect on RA. More than one hundred gene loci associated with RA risk have been identified by single nucleotide polymorphisms (SNPs) [5, 6]. Apart from the human leukocyte antigen (HLA) locus, a well-known genetic www.aging-us.com risk factor for RA, numbers of other susceptibility genes and loci have been characterized [6]. A growing body of non-HLA genetic predisposition studies have been conducted on the association with the risk of RA [7,8,9]
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