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目的系统评价载脂蛋白E(Apo E)基因2个位点(rs7412:C>T;rs429358:T>C)单核苷酸多态性与肝纤维化遗传易感性的关系。方法以“liver cirrhosis”和“Apolipoprotein E”为主题词,辅以“肝硬化”、“肝纤维化”、“Apo E”等关键词,在Pub Med、CNKI等中英文数据库检索相关文献。入选文献为非相关的病例对照研究且数据完整,利用Review Manager5.2和Stata12软件进行合并分析、异质性检验,最后用漏斗图和Egger检验对发表偏倚进行评估。结果最终选定9篇文献,共包含了454例肝纤维化患者和3 048例对照。合并分析显示:Apo Eε2变异与肝纤维化的遗传易感性呈正相关(OR=1.41,95%CI:1.07~1.85),Apo Eε4变异与肝纤维化的遗传易感性呈负相关(OR=0.76,95%CI:0.59~0.99),因合并存在异质性,经随机效应模型分析后显示相关性消失。结论现有研究Meta分析显示Apo E基因变异与肝纤维化有关,但由于研究间异质性的存在,提示需要更多设计合理的研究加入,以提高Meta分析结论的稳定性。
Objective To evaluate the relationship between single nucleotide polymorphisms (SNPs) of rs7412: C> T and rs429358: T> C in two loci of Apo E gene and genetic susceptibility to hepatic fibrosis. Methods With the keywords of “liver cirrhosis” and “Apolipoprotein E” supplemented by keywords such as “liver cirrhosis”, “liver fibrosis” and “Apo E” CNKI and other Chinese and English database search related literature. The selected articles were non-relevant case-control studies with complete data. The data were analyzed using Review Manager 5.2 and Stata 12 software, heterogeneity test, and funnel plot and Egger test were used to evaluate publication bias. Results Nine papers were finally selected and included 454 patients with liver fibrosis and 3048 controls. The pooled analysis showed that there was a positive correlation between Apo Eε2 mutation and genetic susceptibility to hepatic fibrosis (OR = 1.41, 95% CI: 1.07-1.85), and negatively correlated with genetic susceptibility to hepatic fibrosis (OR = 0.76, 95% CI: 0.59 ~ 0.99). Due to the heterogeneity of the merger, the correlation disappeared after analysis by random effect model. Conclusions Meta-analysis of existing research shows that Apo E gene mutation is associated with liver fibrosis. However, due to the heterogeneity of the study, more well-designed studies are needed to improve the stability of Meta analysis.