铁负荷、铁代谢关键基因多态性及其与HBV感染的交互作用与非酒精性脂肪肝的关系

项目名称： 铁负荷、铁代谢关键基因多态性及其与HBV感染的交互作用与非酒精性脂肪肝的关系

项目编号： No.81473047

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 彭仙娥

作者单位： 福建医科大学

项目金额： 60万元

中文摘要： 动物和细胞实验均显示铁超载与非酒精性脂肪肝病（NAFLD）发病机制中所涉及的肝脏脂质代谢紊乱、胰岛素抵抗及氧化应激密切相关，而有关铁超载与NAFLD关系的人群流行病学研究却得到矛盾结果。此外，本课题组前期研究发现HBV与肝细胞脂质代谢紊乱及氧化应激有关，可增加NAFLD的患病风险，而铁和HBV在NAFLD发病过程中是否存在联合作用亟待探讨。本项目在前期工作基础上，采用1：1频数匹配病例－对照研究，对膳食铁的摄入量、血清铁负荷相关指标、铁代谢通路中关键基因的多态性（SNPs）及HBV生物学特征（感染模式、基因型、病毒裁量及Pres区突变等）与NAFLD的关系进行研究；运用多因素统计学方法分析铁负荷，SNPs及HBV在NAFLD发生中的主效应和交互作用。本研究结果不仅有助于进一步阐明NAFLD的发病机制和发现NAFLD危险因素，同时也为人群合理地补铁提供科学依据。

中文关键词： 铁负荷；单核苷酸多态性；HBV感染；非酒精性脂肪肝病；基因-环境交互作用

英文摘要： The development of nonalcoholic fatty liver disease(NAFLD) has been proposed to result from a two-stage process. Firstly, lipid accumulates in the liver, resulting primarily from dietary sources or from the flow of free fatty acids (FFAs) released from adipose tissue. This is frequently associated with IR. The second stage is proposed to result from oxidative stress causing necro-inflammation and cytotoxicity leading to NASH, fibrosis, and ultimately cirrhosis. Iron overload have been implicated in triggering these two stages in vivo and in vitro, indicating that alterations of iron metabolism contributes to the onset of NAFLD and its progression. However, results from epidemiological studies on the association of iron overload with NAFLD remain inconclusive and contradictory. In addition, our preliminary study found that HBV is also associated with NAFLD. However, little is known about whether there is a joint effect between HBV and iron on NAFLD. In this study, we will conduct a case-control study which composed of 1,200 case patients and 1200 age- and sex- frequency matched controls to explore the effects of food intake of iron, plasma iron load, polymorphisms of key genes in iron metabolism and between HBV infection(infection models,HBV genotypes,HBV DNA load and HBV gene mutation) on NAFLD. Multivariable statistical methods will be used to evaluate the potential interactions effects between iron load, gene SNPs and HBV on NAFLD. Our study will not only be helpful for deep understanding of the mechanism involved in NAFLD and finding the risk factors of NAFLD, but also provide scientific evidence for reasonable supplementation of iron in population.

英文关键词： iron load;single nucleotide polymorphism;HBV infection;nonalcoholic fatty liver disease;gene-environment interaction