非酒精性脂肪肝相关基因多态性的研究进展

Research Progress on Gene Polymorphisms Related to Non-alcoholic Fatty Liver Disease

非酒精性脂肪肝(NAFLD)是全球肝脏疾病最常见的原因之一,定义为在无显著饮酒史和其他肝脏疾病的患者中存在≥5%的肝细胞脂肪变性。目前,在全球范围内,NAFLD发病率正以惊人的速度在增长,但其具体的发病机制尚不完全清楚。NAFLD发病机理中,最引人注目的线索来自于人类遗传学。全基因组研究表明,Patatin样磷脂酶域3(PNPLA3)、跨膜6超家族成员2(TM6SF2)、载脂蛋白C3(APOC3)、跨溶血脂酰肌醇酰基转移酶1(MBOAT7)和葡萄糖激酶调节蛋白(GCKR)中不同的单核苷酸多态性(SNPs)对NAFLD的发生和预后有相当大的影响。本文就近年来NAFLD遗传易感性中的5种基因的多态性展开综述,以期对该疾病的发病机制提供新的见解以及对临床提供新的治疗方向。

Non-alcoholic fatty liver disease(NAFLD)is one of the most common causes of liver disease worldwide.It is defined as the presence of≥5%hepatocellular steatosis in patients without a significant history of alcohol consumption and other liver diseases.The prevalence of NAFLD is currently increasing at an alarming rate globally,but its exact pathogenesis is not completely understood.The most compelling clue to the pathogenesis of NAFLD comes from human genetics.Genome-wide studies have shown that different single nucleotide polymorphisms(SNPs)in patatin-like phospholipase domain-containing protein 3(PNPLA3),transmembrane 6 superfamily member 2(TM6SF2),apolipoprotein C3(APOC3),membrane bound O-acyltransferase domain containing 7(MBOAT7)and glucokinase regulatory protein(GCKR)have a considerable impact on NAFLD onset and long-term prognosis.This article reviews the polymorphisms of five genes in the genetic susceptibility of NAFLD in recent years,in order to provide new insights into the pathogenesis of the disease and provide new directions for clinical treatment.