title: PNPLA3 genetic variation in alcoholic steatosis and liver disease progression.
abstract: Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3's function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients.
authors.affiliation: 1 Department of Gastroenterology and Hepatology, University Hospital of Zurich, Switzerland & Hepatology Unit, Clinic Beau-Site, Hirslanden Bern, Bern, Switzerland ; 2 Medical Department I, University Hospital Dresden, TU Dresden, Dresden, Germany ; 3 Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium ; 4 Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium ; 5 Department of Gastroenterology, Paracelsus University of Salzburg, Hospital Oberndorf, Austria ; 6 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.affiliation: 1 Department of Gastroenterology and Hepatology, University Hospital of Zurich, Switzerland & Hepatology Unit, Clinic Beau-Site, Hirslanden Bern, Bern, Switzerland ; 2 Medical Department I, University Hospital Dresden, TU Dresden, Dresden, Germany ; 3 Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium ; 4 Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium ; 5 Department of Gastroenterology, Paracelsus University of Salzburg, Hospital Oberndorf, Austria ; 6 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.affiliation: 1 Department of Gastroenterology and Hepatology, University Hospital of Zurich, Switzerland & Hepatology Unit, Clinic Beau-Site, Hirslanden Bern, Bern, Switzerland ; 2 Medical Department I, University Hospital Dresden, TU Dresden, Dresden, Germany ; 3 Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium ; 4 Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium ; 5 Department of Gastroenterology, Paracelsus University of Salzburg, Hospital Oberndorf, Austria ; 6 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Trépo
authors.affiliation: 1 Department of Gastroenterology and Hepatology, University Hospital of Zurich, Switzerland & Hepatology Unit, Clinic Beau-Site, Hirslanden Bern, Bern, Switzerland ; 2 Medical Department I, University Hospital Dresden, TU Dresden, Dresden, Germany ; 3 Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium ; 4 Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium ; 5 Department of Gastroenterology, Paracelsus University of Salzburg, Hospital Oberndorf, Austria ; 6 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.affiliation: 1 Department of Gastroenterology and Hepatology, University Hospital of Zurich, Switzerland & Hepatology Unit, Clinic Beau-Site, Hirslanden Bern, Bern, Switzerland ; 2 Medical Department I, University Hospital Dresden, TU Dresden, Dresden, Germany ; 3 Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium ; 4 Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium ; 5 Department of Gastroenterology, Paracelsus University of Salzburg, Hospital Oberndorf, Austria ; 6 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Stefano
authors.initials: S
authors.lastname: Romeo
keywords: Genetic risk; host factors; liver cancer; liver cirrhosis