title: Association between the CTLA-4 +49A/G polymorphism and Graves' disease: A meta-analysis.
abstract: The +49A/G polymorphism of the cytotoxic T-lymphocyte-associated antigen-4 gene (CTLA-4) has been associated with Graves' disease (GD). However, results have been inconsistent. The aim of this study was to quantitatively summarize the evidence for CTLA-4 +49A/G polymorphism and GD. Electronic search of PubMed was conducted to select studies. Case-control studies containing available genotype frequencies of CTLA-4 +49 were chosen, and Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. Forty-two case-control studies including 8,288 cases and 9,372 controls were identified. Three studies were eliminated from the total 42 studies due to a p-value <0.05 (p-value for Hardy-Weinberg equilibrium in control group) in these studies which induced significant publication bias. The overall results suggested that the variant genotypes were highly associated (p<0.01) with GD risk in all genetic models (additive model: OR, 1.443; 95% CI, 1.319-1.578; p<0.001; recessive model: OR, 1.589; 95% CI, 1.396-1.808; p<0.001; dominant model: OR, 1.621; 95% CI, 1.430-1.837; p<0.001). Similarly, in the subgroup analyses for ethnicity (Caucasian, Asian), the results were positive. This meta-analysis suggests that the CTLA-4 +49A/G polymorphism is highly associated (p<0.01) with increased risk of GD, especially in Caucasians and Asians. To validate this association, further studies with larger participants worldwide are needed to examine associations between this polymorphism and GD.
authors.affiliation: Faculty of Environmental Science and Engineering and ; Laboratory of Molecular Genetics of Aging and Tumor, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500,  P.R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Si
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Wenru
authors.initials: W
authors.lastname: Tang
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo