CTLA4基因rs231775位点多态性与儿童1型糖尿病关联性的Meta分析  

Association between Rs231775 Polymorphisms of Cytotoxic T Lymphocyte-associated Protein-4 Gene and Risk for Type 1 Diabetes in Children:A Meta-analysis

作　　者：吴静[1] 焦周阳[2] 李瑞珍[3] 罗强 刘玉峰[1] 安金斗[1] 王怀立[1] 李振彪[1] 

机构地区：[1]郑州大学第一附属医院小儿内科,郑州450052 [2]郑州大学第一附属医院心血管外科,郑州450052 [3]武汉市妇女儿童医疗保健中心遗传代谢内分泌科

出　　处：《华中科技大学学报（医学版）》2016年第5期567-573,581,共8页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金青年基金资助项目(No.81300685)

摘　　要：目的系统评价18岁以下年龄组人群中T淋巴细胞毒相关抗原-4（cytotoxic T lymphocyte associated antigen-4,CTLA4）基因rs231775位点多态性（A49G）与1型糖尿病的遗传关联性。方法制定原始文献纳入标准及检索策略,通过计算机检索Pubmed、Highwire Press、Embase、中国知网、万方数据库和维普中文科技期刊数据库,收集截止到2015年12月。根据Cochran Q检验为基础的异质性分析结果,采用随机效应模型借助R-2.7.1软件汇总数据,并选择OR值及其95%CI作为该关联性分析的评估指标,同时采用Egger’s法和Begg’s进行敏感性分析和偏倚估计。结果根据统一的纳入和剔除标准,共纳入16篇文献（包含17个研究数据）,其中儿童1型糖尿病者3 202例,对照组4 348例。多种遗传模型荟萃分析结果显示,CTLA4rs231775位点错义突变能够增加儿童1型糖尿病的发病风险（等位基因分析：OR=1.33,95%CI：1.16-1.53,P〈0.01;加性模型：OR=1.89,95%CI：1.39-2.56,P〈0.01;隐性模型：OR=1.53,95%CI：1.23-1.90,P〈0.01;显性模型：OR=1.41,95%CI：1.17-1.70,P〈0.01）。提示CTLA4rs231775位点多态性与儿童1型糖尿病相关;亚组分析显示研究规模超过300例以上者,CTLA4rs231775位点多态性与儿童1型糖尿病相关。结论大样本数据证实CTLA4rs231775多态性与儿童1型糖尿病发病具有一定相关性,G等位基因是儿童1型糖尿病的危险基因。Objective To evaluate the hereditary association of rs231775 polymorphism of cytotoxic T lymphocyte-associated protein-4（CTLA4）gene with the risk of type 1diabetes mellitus（T1DM）in people under 18 years old.Methods According to the established inclusion criteria for original literatures and the retrieval strategy,search of literatures published until December2015 was performed on PubMed,Highwire Press,Embase,China National Knowledge Infrastructure,Wanfang Database and VIP Chinese Periodical Database.The possibility of heterogeneity was tested by a chi-square-based Q-test.The odds ratio（OR）and its 95% confidence interval（95%CI）were calculated by the random effects model with the aid of R-2.7.1software.Sensitivity analyses were performed to assess the stability of the results,and publication bias was evaluated by using Egger＇s linear regression and Begg＇s test.Results Sixteen eligible studies（seventeen study data）involving 3 202T1DM children and 4 348 healthy controls were included according the uniform inclusion and exclusion criteria.It was found that the missense mutation of rs231775 of CTLA4increased the risk for T1DM in all genetic models（allelic analysis：OR=1.33,95%CI：1.16-1.53,P〈0.01;additive model：OR=1.89,95%CI：1.39-2.56,P〈0.01;recessive model：OR=1.53,95%CI：1.23-1.90,P〈0.01;dominant model：OR=1.41,95%CI：1.17-1.70,P〈0.01）.It was suggested that the polymorphisms of CTLA4rs231775 were closely associated with T1DM children.Subgroup analysis showed that in studies with a large sample size（cases〉300）,there was an association between CTLA4rs231775 polymorphisms and risk of T1DM.Conclusion Large sample data demonstrated an association between CTLA4rs231775 polymorphisms and T1DM among children.CTLA4 Gallele is a risk gene for T1DM in children.

关 键 词：T淋巴细胞毒相关抗原-4 基因多态性 1型糖尿病 儿童 关联性分析 

分 类 号：R725.8[医药卫生—儿科]