Xiaoyu Si1, Xiufeng Zhang, Ying Luo, Wenru Tang. 1. Laboratory of Molecular Genetics of Aging and Tumor, Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, China.
Abstract
BACKGROUND: +49A/G polymorphism of the cytotoxic T-lymphocyte-associated antigen-4 gene (CTLA-4) has been associated with type 1 diabetes (T1D). However, results were inconsistent. The aim of this study was to quantitatively summarize the evidence for CTLA-4 +49A/G polymorphism and T1D. METHODS: Electronic search of PubMed was conducted to select studies. Case-control studies containing available genotype frequencies of CTLA-4 +49 were chosen, and the odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. RESULTS: 49 case-control studies, including 8976 cases and 11012 controls, were identified. 8 studies were eliminated from the total 49 studies because of p<0.05 (p value for Hardy-Weinberg equilibrium in the control group) in these studies, which induce significant publication bias. The overall results suggested that the variant genotypes were highly associated (p<0.01) with T1D risk in all genetic models (additive model: OR 1.345, 95% CI 1.249-1.448, p<0.001; recessive model: OR 1.530, 95% CI 1.370-1.708, p<0.001; dominant model: OR 1.409, 95% CI 1.263-1.572 p<0.001). Similarly, in subgroup analyses for ethnicity (Caucasian, Asian), the results were positive. CONCLUSION: This meta-analysis suggests that the CTLA-4 +49A/G polymorphism is highly associated (p<0.01) with increased risk of T1D, especially in Caucasians and Asians. To validate this association, further studies with more participants worldwide are needed to examine associations between this polymorphism and T1D. Otherwise, we found that the studies of Africans are rare. More studies in Africans are needed especially.
BACKGROUND:+49A/G polymorphism of the cytotoxic T-lymphocyte-associated antigen-4 gene (CTLA-4) has been associated with type 1 diabetes (T1D). However, results were inconsistent. The aim of this study was to quantitatively summarize the evidence for CTLA-4+49A/G polymorphism and T1D. METHODS: Electronic search of PubMed was conducted to select studies. Case-control studies containing available genotype frequencies of CTLA-4 +49 were chosen, and the odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. RESULTS: 49 case-control studies, including 8976 cases and 11012 controls, were identified. 8 studies were eliminated from the total 49 studies because of p<0.05 (p value for Hardy-Weinberg equilibrium in the control group) in these studies, which induce significant publication bias. The overall results suggested that the variant genotypes were highly associated (p<0.01) with T1D risk in all genetic models (additive model: OR 1.345, 95% CI 1.249-1.448, p<0.001; recessive model: OR 1.530, 95% CI 1.370-1.708, p<0.001; dominant model: OR 1.409, 95% CI 1.263-1.572 p<0.001). Similarly, in subgroup analyses for ethnicity (Caucasian, Asian), the results were positive. CONCLUSION: This meta-analysis suggests that the CTLA-4+49A/G polymorphism is highly associated (p<0.01) with increased risk of T1D, especially in Caucasians and Asians. To validate this association, further studies with more participants worldwide are needed to examine associations between this polymorphism and T1D. Otherwise, we found that the studies of Africans are rare. More studies in Africans are needed especially.