Meta-analysis of Association Between the+49A/G Polymorphism of Cytotoxic T-Lymphocyte Antigen-4 and Thyroid Associated Ophthalmopathy

Purpose of the study: Cytotoxic-T lymphocyte antigen-4 (CTLA-4) has been shown to play an important role in the development and progression of thyroid associated ophthalmopathy (TAO). A number of case-control studies focused on the association between CTLA-4 + 49A/G polymorphism and risk for TAO. But the results were not always consistent. So we performed a meta-analysis to evaluate the precise association between this polymorphism and risk for TAO. Materials and methods: All publications on the association between CTLA-4 +49A/G polymorphism and TAO were searched in the following electronic databases: PubMed, Embase, the Cochrane library and Chinese Biomedical Literature Database, with the last report up to May 2014. This meta-analysis was assessed by Review Manager 5.1. Results: A total of 14 studies were involved in this meta-analysis, including 1128 cases and 2539 controls. Overall, we found a significant association between CTLA-4 +49A/G polymorphism and TAO (G versus A: OR = 1.64, 95% CI = 1.40-1.92, p < 0.00001; GG versus AG+ AA: OR = 2.02, 95% CI = 1.59-2.57, p < 0.00001; GG + AG versus AA: OR = 2.01, 95% CI = 1.66-2.43, p < 0.00001; GG versus AA: OR = 2.74, 95% CI = 1.83-4.10, p < 0.00001; AG versus AA: OR = 1.75, 95% CI = 1.42-2.15, p < 0.00001). The results were not materially altered after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded. Significant association was also detected in both Caucasian and Asian populations in subgroup analysis divided by different ethnicity. Conclusion: Our meta-analysis supports the association between the CTLA-4 +49A/G polymorphism and TAO.