Wang Bo, Du Wei, Jia Yutao, Zhang Xiaobai, Ma Guorui
Department of Paediatrics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
Department of Medical Laboratory, Luoyang Central Hospital, Luoyang, Henan, China.
Oncotarget. 2017 Feb 7;8(6):10553-10564. doi: 10.18632/oncotarget.14457.
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.
1型糖尿病（T1D）是一种与多种基因变异相关的遗传性疾病。本系统评价和荟萃分析评估了细胞毒性T淋巴细胞相关蛋白4（CTLA-4）+49A/G多态性与儿童T1D风险之间的相关性。采用随机效应模型估计相关比值比（OR）和95%置信区间（CI）。试验序贯分析（TSA）用于确定当前可用证据是否充分和确凿。我们的结果表明，CTLA-4基因多态性在等位基因模型（G vs. A：OR=1.33，95%CI=1.19-1.48；I2=44.0%，异质性P=0.001）和共显性模型（GG vs. AA：OR=1.75，95%CI=1.37-2.24；I2=57.5%，异质性P=0.001；GA vs. AA：OR=1.26，95%CI=1.09-1.46；I2=40.4%，异质性P=0.036）中显著增加了儿童T1D的风险。亚组分析结果表明，亚洲人群的OR值（等位基因模型OR=1.60，GG vs. AA的OR=2.46，GA vs. AA的OR=1.58）高于白种人群（等位基因模型OR=1.24，GG vs. AA的OR=1.55，GA vs. AA的OR=1.19）。TSA结果表明效应证据充分。总之，CTLA4 +49A/G多态性增加了儿童T1D的风险，CTLA4 +49A/G可被认为是儿童T1D的一个遗传标志物。
