PNPLA3 I148M polymorphism and progressive liver disease  

作　　者：Paola Dongiovanni Benedetta Donati Roberta Fares Rosa Lombardi Rosellina Margherita Mancina Stefano Romeo Luca Valenti 

机构地区：[1]Internal Medicine,Fondazione IRCCS Ca’ Granda Ospedale Policlinico Milano,Department of Pathophysiology and Transplantation,Università degli Studi di Milano,20122 Milano,Italy [2]Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory,Department of Molecular and Clinical Medicine,University of Gothenburg,40530 Gothenburg,Sweden [3]Clinical Nutrition Unit,Department of Medical and Surgical Sciences,University Magna Graecia,88100 Catanzaro,Italy

出　　处：《World Journal of Gastroenterology》2013年第41期6969-6978,共10页世界胃肠病学杂志（英文版）

基　　金：Supported by Associazione Malattie Metaboliche del Fegato ONLUS(Non-profit organization for the Study and Care of Metabolic Liver Diseases);Centro Studi Malattie Metaboliche del Fegato,Universitàdegli Studi di Milano

摘　　要：The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.The 148 Isoleucine to Methionine protein variant (I148M) of patatin-like phospholipase domain-containing 3 (PNPLA3), a protein is expressed in the liver and is involved in lipid metabolism, has recently been identified as a major determinant of liver fat content. Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver: from simple steatosis to steatohepatitis and progressive fibrosis. Furthermore, the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis, and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis, and possibly chronic hepatitis B virus hepatitis, hereditary hemochromatosis and primary sclerosing cholangitis. All in all, studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases. Remarkably, the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation, suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes, directly promoting fibrogenesis. Therefore, PNPLA3 is a key player in liver disease progression. Assessment of the I148M polymorphism will possibly inform clinical practice in the future, whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.

关 键 词：Alcoholic LIVER DISEASE Chronic HEPATITIS C virus HEPATITIS FIBROGENESIS Genetics Hepatocellular carcinoma LIVER DISEASE Nonalcoholic fatty LIVER DISEASE Patatin-like PHOSPHOLIPASE domain-containing 3 Single nucleotide POLYMORPHISM Steatosis 

分 类 号：R575[医药卫生—消化系统]