Research Papers:

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

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

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Oncotarget. 2017; 8:10553-10564. https://doi.org/10.18632/oncotarget.14457

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Bo Wang1,*, Wei Du2,*, Yutao Jia1, Xiaobai Zhang1, Guorui Ma1

1Department of Paediatrics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China

2Department of Medical Laboratory, Luoyang Central Hospital, Luoyang, Henan, China

*These authors have contributed equally to this work

Correspondence to:

Guorui Ma, email: [email protected]

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


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; I2=44.0% and P=0.001for heterogeneity) and a codominant model (GG vs. AA: OR=1.75, 95%CI=1.37-2.24; I2=57.5% and P=0.001for heterogeneity; GA vs. AA: OR=1.26, 95%CI=1.09-1.46; I2=40.4% and P=0.036for heterogeneity). Subgroup analysis results indicated that the ORs were higher in the Asian population (ORallelic model=1.60, ORGG vs. AA=2.46 and ORGA vs. AA=1.58) than the Caucasian population (ORallelic model==1.24, ORGG vs. AA=1.55 and ORGA 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.

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