我国儿童HLA-DQA1基因多态性与幽门螺杆菌感染关系的Meta分析

Meta-analysis on Relationship between HLA-DQA1 Gene Polymorphism and Helicobacter Pylori Infection in Chinese Children

目的采用Meta分析的方法综合评价中国儿童HLA-DQA1基因多态性与幽门螺杆菌(Hp)感染的关联性。方法以"幽门螺杆菌""HLA-DQA1""基因多态性""儿童"为检索词,从中国生物医学文献数据库(CBMdisc)、清华同方(CNKI)系列数据库、维普数据库(VIP)、万方数据库、Pubmed和Medline数据库,全面检索1995年1月至2015年1月国内外正式刊物上公开发表的有关HLA-DQA1与中国儿童Hp感染的病例对照研究的文献,应用Rev Man 5.0软件对符合筛选标准的研究以OR值作为效应指标,根据异质性检验结果选择相应模型进行综合定量分析。结果符合纳入标准的共11项病例对照研究,共计Hp感染组445例和正常对照组317例。对11项研究中涉及较多的HLA-DQA1*0101,0102,0103,0104,0201,0301,0302,0401,0501,0601共10个位点进行了Meta分析。经综合分析:1HLA-DQA1*0103和HLA-DQA1*0301可能为中国儿童Hp感染的易患性基因OR合并及其95%CI分别为1.77(1.18,2.64),P=0.005;1.80(1.09,2.98),P=0.02;2HLADQA1*0104和HLA-DQA1*0302位点存在异质性,按民族进行亚组分析,结果为:对于HLA-DQA1*0104,HLA-DQA1*0302位点汉族组间无异质性,而少数民族组仍有异质性,亚组结果显示,HLADQA1*0302可能是我国汉族儿童的保护基因[OR合并及其95%CI为0.50(0.26,0.98),P=0.040];HLA-DQA1*0104可能是少数民族儿童感染易患基因[OR合并及其95%CI为2.15(2.13,3.77),P=0.007];3换用模型对其进行敏感性分析显示,除HLA-DQA1*0104和HLA-DQA1*0301两位点结论发生改变外,其余位点结论均未发生变化。而剔除小样本后进行敏感性分析显示结论均未发生改变。敏感性分析结果表明结果较可靠。结论中国儿童Hp感染可能与HLA-DQA1*0103和HLADQA1*0301位点有关联,未发现其余位点与感染有关。

Objective To assess the associations of HLA-DQA1 gene polymorphism with Helicobacter pylori（Hp） infection in Chinese children through meta-analysis. Methods Articles published from 1995 to 2015 on the relationship between HLA-DQA1 gene polymorphism and Helicobaeter pylori infection were searched from CBMdisc, CNKI database, VIP database, Wanfang database, Pubmed and Medline, using the searching terms of ＂Helicobacter pylori＂ ＂HLA-DQA1 gene polymorphism＂ ＂ children＂, etc. The results were quantitatively analyzed by RevMan 5.0 seftware,the pooled odds ratio（OR） were calculated by choo- sing FLxed effect model or random effect mode,according to the result of Heterogeneity test. Results A total of 445 children with Helicabacter pylori infection and 317 uninfected healthy controls were included from 11 studies. Meta-analysis were conducted in the following gene loci：HLA-DQA1 ＊ 0101,0102,0103,0104,0201, 0301,0302,0401,0501,0601. After comprehensive analysis ： ①HIA-DQA1 ＊ 0103 and HLA-DQA1 ＊ 0301 alleles were the risk factors of Hp infection,the values of pooled odds ratio were 1. .77（95% CI 1.18-2. 64, P = 0. 005 ） and 1.80 （ 95 % CI 1.09-2.98, P = 0.02 ） respectively. ②Subgroup-analysis： the results of sub- group analyses based on nationality showed ：for HLA-DQA1 ＊ 0104 and HLA-DQA1 ＊ 0302 no heterogeneity was observed in Han nationality group, but not in minority group as to HLA-DQA1 ＊ 0302. In addition, statis- tical difference was found after subgroup analyses in the Han nationality group. HLA-DQA1 ＊ 0302 alleles were the protection factors against Hp infection, and the values of pooled odds ratio were 0.50 （95 % CI 0. 26- 0. 98 ,P =0.04）. HLA-DQA1 ＊ 0104 alleles were the susceptible factors against helicobacter pylori infection in the minorities, and the values of pooled odds ratio were 2.15 （95 % CI 2. 13 -3.77, P = 0. 007 ）. ③Sensitiv- ity analysis ： almost all the conclusions were not changed except for the DQA1 ＊ 0104 and DQA1 ＊ 0301 when changing statistical model, while sensitivity analysis did not change the conclusions after removing the small sample, showing that the results were reliable. Conclusion The occurrence of Hp infection is associated with the gene polymorphism of HLA-DQA1 ＊ 0103, ＊ 0301 in Chinese children, while no correlations with other loci are observed.