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Cytotoxic T-lymphocyte-associated protein 4 +49A/G polymorphisms contribute to the risk of type 1 diabetes in children: An updated systematic review and meta-analysis with trial sequential analysis

2017; Impact Journals LLC; Volume: 8; Issue: 6 Linguagem: Inglês

10.18632/oncotarget.14457

1949-2553

Bo Wang, Wei Du, Yutao Jia, Xiaobai Zhang, Guorui Ma,

Diabetes Management and Research

// Bo Wang 1, * , Wei Du 2, * , Yutao Jia 1 , Xiaobai Zhang 1 , Guorui Ma 1 1 Department of Paediatrics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China 2 Department of Medical Laboratory, Luoyang Central Hospital, Luoyang, Henan, China * These authors have contributed equally to this work Correspondence to: Guorui Ma, email: aquacity@126.com Keywords: type 1 diabetes, cytotoxic T-lymphocyte associated protein 4, polymorphism, risk, meta-analysis Received: October 05, 2016 Accepted: December 13, 2016 Published: January 02, 2017 ABSTRACT Type 1 diabetes (T1D) is a heritable disease associated with multiple genetic variants. This systematic review and meta-analysis assessed the correlation between cytotoxic T-lymphocyte-associated protein 4(CTLA-4) +49A/G polymorphisms and the risk of T1D in children. The random effects model was used to estimate the related odds ratios (ORs) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was used to determine whether the currently available evidence was sufficient and conclusive. Our results indicated that CTLA-4 gene polymorphisms significantly increased the risk of childhood T1D in an allelic model (G vs. A: OR=1.33, 95%CI=1.19-1.48; I 2 =44.0% and P =0.001for heterogeneity) and a codominant model (GG vs. AA: OR=1.75, 95%CI=1.37-2.24; I 2 =57.5% and P =0.001for heterogeneity; GA vs. AA: OR=1.26, 95%CI=1.09-1.46; I 2 =40.4% and P =0.036for heterogeneity). Subgroup analysis results indicated that the ORs were higher in the Asian population (OR allelic model =1.60, OR GG vs. AA =2.46 and OR GA vs. AA =1.58) than the Caucasian population (OR allelic model ==1.24, OR GG vs. AA =1.55 and OR GA vs. AA =1.19). The TSA results indicated that the evidence of the effect was sufficient. In conclusion, CTLA4 +49A/G polymorphisms increased the risk of T1D in children, and CTLA4 +49A/G can be considered to be a genetic marker for T1D in children.