title: The Genetics of Nonalcoholic Fatty Liver Disease: Spotlight on PNPLA3 and TM6SF2.
abstract: Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum that spans simple steatosis, through nonalcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis. Nonalcoholic fatty liver disease is characterized by substantial interpatient variation in rate of progression and disease outcome: Although up to 25% of the general population are at risk of progressive disease, only a minority experience associated liver-related morbidity. Nonalcoholic fatty liver disease is considered a complex disease trait that occurs when environmental exposures act upon a susceptible polygenic background composed of multiple independent modifiers. Recent advances include the identification of PNPLA3 as a modifier of disease outcome across the full spectrum of NAFLD from steatosis to advanced fibrosis and hepatocellular carcinoma; and the discovery of TM6SF2 as a potential "master regulator" of metabolic syndrome outcome, determining not only risk of advanced liver disease, but also cardiovascular disease outcomes. In this article, the authors will review the field, discussing in detail the current status of research into these important genetic modifiers of NAFLD progression.
authors.affiliation: Liver Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Quentin M
authors.initials: QM
authors.lastname: Anstee
authors.affiliation: Liver Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
mesh_terms: D000818:Animals; D018450:Disease Progression; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D010641:Phenotype; D011379:Prognosis; D012307:Risk Factors; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D005819:Genetic Markers; D008049:Lipase; D008565:Membrane Proteins; C419195:TM6SF2 protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent