非酒精性脂肪性肝病基因多态性的巢式病例-对照研究

A nested case-control study on genetic polymorphisms for patients with non-alcoholic fatty liver disease

目的探讨广东省汉族人中代谢综合征（MS）相关基因多态性和非酒精性脂肪性肝病（NAFLD）发病易感性的关系。方法在广东省流行病学调查中抽取符合中华医学会肝病学分会诊断标准，且B超、临床和实验室检查结果为典型的成年NAFLD患者50～117例，采用巢式病例对照方法，现场按1：1匹配，选择非NAFLD人群作对照。各受试者均由静脉血中提取DNA，采用聚合酶链式反应-限制性片段长度多态性（PCR—RFLP）法检测7个候选基因9个位点单核苷酸多态性（SNP）。结果基因SNP和NAFLD的发病易感性相关。正相关的因子（即增加易感性）为：肿瘤坏死因子-α（TNF—α）-238、脂联素-45、瘦素-2548、过氧化物酶体增殖物激活受体-γ—161、磷脂酰乙醇胺N-甲基转移酶-175。负相关的因子（即降低易感性）为：脂联素-276、肝脂肪酶514。不相关的因子为：TNF—α-380、PPAR共激活因子-1α-482。结论多数MS相关的细胞因子基因SNP和NAFLD发病易感性相关。

Objective To investigate the relationship between the genetic polymorphisms, which played roles in the pathogenesis of metabolic syndrome （MS）, and susceptibility of non-alcoholic fatty liver disease （NAFLD） in Han people in Guangdong province. Methods The subjects were selected from an epidemiologic survey in Guangdong province. Fifty to 117 adult NAFLD patients, who met the criteria of Chinese guideline for diagnosis of NAFLD and had typically clinical, biochemical signs and abdominal ultrasonography, were recruited in the study. By using 1 ： 1 matched method of nested case-control study, same numbers of people without NAFLD were included as controls. The genetic analyses was performed by using genomic DNA extracted from peripheral blood. Polymerase chain reaction （PCR）-restriction fragment length polymorphism （RFLP） was applied to detect the single nucleotide polymorphisms （SNPs） at 9 sites in 7 candidate genes. Results Most SNPs of the genes were related to the susceptibility of NAFLD. Some of them had positive relation （increasing the risk） such as tumor necrosis factor （ TNF）-α-238, adiponectin-45, leptin-2548, peroxisome proliferator-activated receptors （ PPAR ） 7-161 and phosphatidylethanolamine N- methyltransferase （PEMT）-175. Some had negative relation （decreasing the risk） including adiponectin 276 and hepatic lipase-514. And some had no relation （TNF-α-380 and PPAR g coactivator-1α 482）. Conclusion Most cytokines＇ SNPs of candidate genes discovered in MS patients are related to the susceptibility of NAFLD.