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Critical Reviews™ in Eukaryotic Gene Expression
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Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.2020034872
pages 377-390

Meta-Analysis of CTLA-4 +49 Gene Polymorphism and Susceptibility to Graves' Disease

Fengli Huang
Department of Endocrinology, Hematology and Nephrology of Zhongwei People's Hospital of Ningxia, Zhongwei, Ningxia, China
Qin He
Department of Endocrinology, Hematology and Nephrology of Zhongwei People's Hospital of Ningxia, Zhongwei, Ningxia, China
Xiaoli Jiao
Department of Endocrinology, Hematology and Nephrology of Zhongwei People's Hospital of Ningxia, Zhongwei, Ningxia, China
Hong Zhang
Department of Endocrinology, Hematology and Nephrology of Zhongwei People's Hospital of Ningxia, Zhongwei, Ningxia, China
Qing Chang
Key Laboratory of Fertility Preservation and Maintenance (NXMU), Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, China


Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays an important role in the initiation and development of Graves' disease (GD), especially CTLA-4 +49A/G polymorphism and genetic susceptibility to GD. However, the current conclusions are consistent. Therefore, this study adopted meta-analysis method to assess the exact correlation between this polymorphism and GD risk.
Methods: Literature searches were performed in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Wanfang, and other databases for data on the correlation between polymorphisms of CTLA-4 +49A/G and GD risk. The end date for publications was May 2020. Stata 15.0 software was used for data analysis.
Results: A total of 33 papers were included, covering 8,555 cases and 9,533 controls. The results showed that the CTLA-4 +49 allele G compared to allele A, odds ratio (OR) = 1.62, 95% CI [1.56, 2.09]. In the dominant, recessive, homozygous, and heterozygous genetic models, comparing the GD group and the control group, the combined OR was 1.81, 95% CI [1.56, 2.09]; 1.91, 95% CI [1.66, 2.21]; 2.75, 95% CI, [2.21, 3.41]; and 1.49, 95% CI [1.29, 1.71], respectively. When it was analyzed by dividing genetic models into subgroups according to ethnicity and published year, the data the of genetic model in each subgroup were also statistically significant.
Conclusion: The CTLA-4 +49A/G polymorphism was strongly associated with genetic susceptibility to GD. Allele G, genotypes GG, GG + GA, and GA are correlated with an increase in the risk of GD.


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