中国人群CTLA-4基因第49位点和CT60位点多态性与毒性弥漫性甲状腺肿相关性的Meta分析

Meta analysis on the correlation between polymorphism of A49G and CT60 of CTLA-4 gene and Graves′disease among Chinese population

目的系统评价中国人群弥漫性毒性甲状腺肿（Graves′disease,GD）与细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因外显子1＋49位点A/G（A49G）和3′非翻译区A/G（CT60）多态性的相关性。方法通过中国学术期刊全文数据库（CNKI）、PubMed数据库、万方数据库、中国生物医学文献数据库（CBM）,收集国内外关于中国人群细胞毒性T淋巴细胞相关抗原-4（CTLA-4）基因A49G和CT60位点多态性与GD病相关性的病例对照研究,通过严格筛选文献,评价文献质量,提取所需文献原始数据,用RevMan5.3软件和Stata12.0软件进行Meta分析和Egger′s线性回归检验,分别统计描述基因频率模型（G vs A）、共显性模型（GG vs AA）、显性模型（GG＋AG vs AA）、隐性模型（GG vs AG＋AA）的合并OR值及95%CI。结果入选文献25篇,中文16篇,英文9篇。CTLA-4基因A49G多态性的基因频率模型、共显性模型、显性模型、隐性模型合并OR值（95%CI）分别是1.94（1.67-2.25）、3.93（2.84-5.45）、2.69（2.07-3.50）、2.09（1.73-2.53）;CTLA-4基因CT60位点多态性的基因频率模型、共显性模型、显性模型、隐性模型合并OR值（95%CI）分别是1.38（1.26-1.51）、1.61（1.28-2.03）、1.58（1.26-1.97）、1.40（1.26-1.56）。结论 GD病与CTLA-4基因A49G和CT60位点多态性有关,且为正相关,即两位点多态性是GD病发病的危险因素。

Objective To systematically evaluate the correlation between the polymorphism of exon-1A49Gand3′untranslated region of A/G（CT60）of cytotoxic T lymphocytes associated antigen-4（CTLA-4）gene and Graves′disease（GD）in Chinese population. Methods Case-control studies on the correlation of polymorphism of A49 Gand CT60of CTLA-4gene with GD were searched in the databases of CNKI,PubMed,Wanfang database,CBM based on the keywords of Graves′disease,Graves,CTLA-4polymorphism and literatures were chosen according to the inclusion and exclusion criteria.Meta-analysis and Egger liner regression text were performed using RevMan 5.3software and Stata12.0software.The pooled ORvalue and 95%CI were calculated with G vs A,GG vs AA,GG＋AG vs AA,and GG vs AG＋AA genetic models. Results A total of 25 literatures were included in the meta-analysis.The pooled ORs（95% CIs）were 1.94（1.67-2.25）,3.93（2.84-5.45）,2.69（2.07-3.50）and 2.09（1.73-2.53）for the four genetic models of A49 G,and were1.38（1.26-1.51）,1.61（1.28-2.03）,1.58（1.26-1.97）and 1.40（1.26-1.56）for the four genetic models of CT60. Conclusions The meta-analysis demonstrates that A49 Gand CT60polymorphisms of CTLA-4gene are closely associated with GD and are risk factors of GD in Chinese population.