HFE基因C282Y、H63D多态性与非酒精性脂肪性肝病、肝硬化及肝细胞癌风险的关联：对5758例病例和14741例对照的最新系统评价和荟萃分析
Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls.
作者信息
Ye Qing, Qian Bao-Xin, Yin Wei-Li, Wang Feng-Mei, Han Tao
机构信息
The Third Central clinical college of Tianjin Medical University, Tianjin, PR China.
Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, PR China.
出版信息
PLoS One. 2016 Sep 22;11(9):e0163423. doi: 10.1371/journal.pone.0163423. eCollection 2016.
BACKGROUND
Conflicting results have been obtained for the association between two common polymorphisms (C282Y, H63D) of human HFE (hereditary hemochromatosis) gene and the risks of the liver diseases, including non-alcoholic fatty liver disease (NAFLD), liver cirrhosis and hepatocellular carcinoma (HCC).
METHODS
An updated systematic review and meta-analysis was conducted to evaluate the potential role of HFE polymorphisms in the susceptibility to NAFLD, liver cirrhosis and HCC. After retrieving articles from online databases, eligible studies were enrolled according to the selection criteria. Stata/SE 12.0 software was utilized to perform the statistical analysis.
RESULTS
In total, 43 articles with 5,758 cases and 14,741 controls were selected. Compared with the control group, a significantly increased risk of NAFLD was observed for the C282Y polymorphism in the Caucasian population under all genetic models and for the H63D polymorphism under the allele, heterozygote and dominant models (all OR>1, Passociation<0.05). However, no significant difference between liver cirrhosis cases and the control group was observed for HFE C282Y and H63D (all Passociation>0.05). In addition, we found that HFE C282Y was statistically associated with increased HCC susceptibility in the overall population, while H63D increased the odds of developing non-cirrhotic HCC in the African population (all OR>1, Passociation<0.05). Moreover, a positive association between compound heterozygosity for C282Y/H63D and the risk of NAFLD and HCC, but not liver cirrhosis, was observed.
CONCLUSION
Our meta-analysis provides evidence that the HFE C282Y and H63D polymorphisms confer increased genetic susceptibility to NAFLD and HCC but not liver cirrhosis. Additional well-powered studies are required to confirm our conclusion.
背景
人类HFE（遗传性血色素沉着症）基因的两种常见多态性（C282Y、H63D）与包括非酒精性脂肪性肝病（NAFLD）、肝硬化和肝细胞癌（HCC）在内的肝脏疾病风险之间的关联研究结果相互矛盾。
方法
进行了一项更新的系统评价和荟萃分析，以评估HFE多态性在NAFLD、肝硬化和HCC易感性中的潜在作用。从在线数据库检索文章后，根据选择标准纳入符合条件的研究。使用Stata/SE 12.0软件进行统计分析。
结果
共选择了43篇文章，包含5758例病例和14741例对照。与对照组相比，在所有遗传模型下，白种人群中C282Y多态性以及在等位基因、杂合子和显性模型下H63D多态性的NAFLD风险显著增加（所有OR>1，P关联<0.05）。然而，HFE C282Y和H63D在肝硬化病例与对照组之间未观察到显著差异（所有P关联>0.05）。此外，我们发现HFE C282Y在总体人群中与HCC易感性增加存在统计学关联，而H63D在非洲人群中增加了非肝硬化HCC的发病几率（所有OR>1，P关联<0.05）。此外，观察到C282Y/H63D复合杂合性与NAFLD和HCC风险呈正相关，但与肝硬化风险无关。
结论
我们的荟萃分析提供了证据，表明HFE C282Y和H63D多态性增加了对NAFLD和HCC的遗传易感性，但与肝硬化无关。需要更多有足够效力的研究来证实我们的结论。
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