title: Genetics of Alcoholic Liver Disease.
abstract: Excess alcohol consumption with consequent alcoholic liver disease (ALD) is a common cause of liver dysfunction and liver-related mortality worldwide. However, although the majority of heavy drinkers will develop steatosis, only a minority progress to advanced liver disease and cirrhosis. Thus, ALD is a complex disease where subtle interpatient genetic variations and environmental factors interact to determine disease progression. One genome-wide association study specifically addressing genetic modifiers of ALD has been published. However, most of our understanding is based on studies conducted on nonalcoholic fatty liver disease. Translation of candidates from these studies into ALD has established a role for variants in genes including PNPLA3 and potentially TM6SF2 across the disease spectrum from steatosis, through cirrhosis to hepatocellular carcinoma. Here the authors review the current status of the field with a particular focus on recent advances.
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: Ann K
authors.initials: AK
authors.lastname: Daly
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: D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D018450:Disease Progression; D000431:Ethanol / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007109:Immunity / Q000235:genetics; D008049:Lipase / Q000235:genetics; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics; D008108:Liver Diseases, Alcoholic / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D009435:Synaptic Transmission / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000431:Ethanol; D008049:Lipase; D008565:Membrane Proteins; D051197:Toll-Like Receptor 4; C495345:TLR4 protein, human; C419195:TM6SF2 protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent