HFE基因多态性与非酒精性脂肪肝病遗传易感性的Meta分析

目的 采用Meta分析方法综合评价HFE基因多态性与非酒精性脂肪肝病(NAFLD)遗传易感性之间的关系.方法 检索PubMed、EMBASE、中国知网和万方数据库,获取2016年12月之前发表的关于C282Y和H63D多态性与NAFLD的病例-对照研究.以OR及95% CI为效应指标,应用Stata 12.0软件进行Meta分析、敏感性分析及发表偏倚评价.结果 共纳入17项研究,包含2 181例NAFLD病例和7 921例对照.采用随机效应模型和固定效应模型分别对C282Y和H63D进行合并分析.C282Y、H63D杂合基因型的合并OR分别为1.87(95% CI=1.12-3.12)、1.22(95% CI=1.05-1.41);显性模型合并OR值分别为1.95(95% CI=1.14-3.31)、1.24(95% CI=1.07-1.43).而在根据研究人群进行分层分析时发现,C282Y仅在高加索人中表现出与NAFLD发病的统计学关联,亚洲人群中则不存在该多态性;H63D的突变等位基因增加NAFLD发病风险的效应也仅限于高加索人群和混合人群.此外,研究未观察到发表偏倚,且敏感性分析表明结果稳定.结论 HFE基因的C282Y、H63D多态性可增加NAFLD发病风险,但其致病效应主要出现在高加索人群中.

Relationship between HFE polymorphisms and genetic susceptibility of nonalcoholic fatty liver disease:a Meta-analysis

Objective To evaluate the correlation between the HFE polymorphisms (C282Y and H63D) and the susceptibility of nonalcoholic fatty liver disease (NAFLD).Methods The relevant literatures in PubMed,EMBASE,China National Knowledge Internet and Wanfang databases before Dec,2016 were collected.Odds ratio (OR) and 95% confidence intervals (95% CI) were applied as the effects estimates.The pooled analysis,sensitivity analysis and publication bias were performed in the software Stata V12.0.Results Seventeen studies with 2181 cases and 7921 controls were included in this Meta-analysis.The C282Y and H63D were both significantly with the risk of NAFLD,with the OR of 1.87 (95% CI=1.12-3.12) and 1.22 (95% CI=1.05-1.41) for the heterozygotes,respectively.Similarly,the OR were 1.95 (95% CI=1.14-3.31) and 1.24 (95% CI=1.07-1.43) for the dominant model,respectively.When performed the stratified analysis by the study populations,the significant genetic association of C282Y was only seen in Caucasian population,whereas this polymorphism did not exist in the Asian population.In the Caucasian and mixed populations,we also observed the significant association of H63D,whereas there was no significant association in the Asian population.No significant publication bias was found,and sensitivity analysis suggested the robust stability of the current results.Conclusion This Meta-analysis suggests that the variants of C282Y and H63D) in HFE gene could increase the risk of NAFLD,but the detrimental effect seems to be mainly existed in the Caucasian population.