血管紧张素转换酶基因多态性与儿童原发性肾病综合征关联性的系统评价和Meta分析

目的 系统评价血管紧张素转换酶（ACE）基因多态性与儿童原发性肾病综合征（PNS）的关联。方法 计算机检索PubMed、EMBASE、Wiley Online Library、Cochrane图书馆、Science Citation Index、Google Scholar、中国期刊全文数据库、万方数据库、中国生物医学文献数据库和维普数据库，检索时间为2000年1月1日至2014年5月31日，纳入ACE基因多态性与儿童PNS关联的病例对照研究。提取PNS组和对照组基因型和等位基因频率，计算各纳入文献对照组Hardy Weinberg平衡（HWE），并进行文献偏倚评价。采用Stata 12.0软件，对PNS组和对照组ACE基因DD、DI、II基因型和D、I等位基因频率的差异行Meta分析。结果 14篇文献进入Meta分析，共纳入2 849例研究对象，其中PNS组1 264例，对照组1 585例。14篇文献偏倚风险较大。①D等位基因频率PNS组高于对照组（OR=1277，95%CI 1080~1509，P=0004）；I等位基因频率PNS组低于对照组（OR=0811，95%CI 0738~0892，P＜0001）。②DD基因型频率PNS组高于对照组（OR=1505，95%CI 1136~1994，P=0004）；II基因型频率PNS组低于对照组（OR=0746，95%CI 0634~0877，P＜0001）；DI基因型频率PNS组与对照组差异无统计学意义（OR=0932，95%CI 0805~1079，P=0347）。③6篇文献对照组不符合HWE，剔除后8篇文献行敏感性分析，结果无明显变化；④DD基因型和D等位基因的文献间具有异质性，对照人群的来源、种族可解释部分的异质性，HWE与否不是异质性的原因。结论 ACE基因DD基因型和D等位基因与儿童PNS的关联性不确定，如果有关联，强度可能较低。

Relationship between ACE gene polymorphisms and pediatric idiopathic nephrotic syndrome: a meta-analysis

Objective To assess the relationship between angiotensin converting enzyme (ACE) gene polymorphism and pediatric idiopathic nephrotic syndrome (PNS). Methods Case-control studies searched from the database of PubMed, EMBASE, Wiley Online Library, Cochrane Library, Science Citation Index, Google Scholar, China National Knowledge Infrastucture, Wanfang Data, China Biology Medicine, China science and technology journal were recruited to summarize the association between ACE gene polymorphisms with PNS from January 2000 to May 2014. Meta-analysis of the frequency of D, I alleles and DD, DI, II genotypes between PNS group and the control group were performed by Stata 12.0 software. Results Fourteen literatures including 2 849 subjects (1 264 in PNS group and 1 585 in the control group) were recruited. ① The frequency of D allele in PNS group was higher than that in the control group （OR=1.277，95%CI 1.080-1.509，P=0.004）and the frequency of I allele in PNS group was lower than that in the control group (OR=0.811，95%CI 0.738-0.892，P＜0.001). ② The frequency of DD genotype in PNS group was higher than that in the control group (OR=0.746，95%CI 0.634-0.877，P＜0.001), the frequency of II genotype in PNS group was lower than that in the control group (OR=0.746，95%CI 0.634-0.877，P＜0.001) and there was no significant difference of the frequency of DI genotype between PNS and the control groups. ③ Six literatures did not meet Hardy-Weinberg equilibrium, but it did not bias the study by sensitive analysis. ④ The articles reported D allele and DD genotype showed significant heterogeneity. The control group and race could explain partial heterogeneity, but Hardy-Weinberg equilibrium was not the cause of heterogeneity. Conclusion The relation about DD gene and D allele with PNS was not indubitable. The strength of the association about ACE gene and PNS gene was possibly lower.