title: Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review.
abstract: OBJECTIVE
  To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.
  
  
  METHODS
  The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur.
  
  
  RESULTS
  We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine.
  
  
  CONCLUSIONS
  Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.
authors.affiliation: Tyler J Severson, Herbert L Bonkovsky, Department of Gastroenterology and Hepatology, Wake Forest University NC Baptist Medical Center, Winston-Salem, NC 27157, United States.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Severson
authors.affiliation: Tyler J Severson, Herbert L Bonkovsky, Department of Gastroenterology and Hepatology, Wake Forest University NC Baptist Medical Center, Winston-Salem, NC 27157, United States.
authors.forename: Siddesh
authors.initials: S
authors.lastname: Besur
authors.affiliation: Tyler J Severson, Herbert L Bonkovsky, Department of Gastroenterology and Hepatology, Wake Forest University NC Baptist Medical Center, Winston-Salem, NC 27157, United States.
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics; D020022:Genetic Predisposition to Disease; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism; D008049:Lipase / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D002787:Sterol Esterase / Q000235:genetics; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D051547:Heme Oxygenase-1; D007501:Iron; D008049:Lipase; D008565:Membrane Proteins; D002787:Sterol Esterase; C419195:TM6SF2 protein, human; C526492:FTO protein, human; C496541:HMOX1 protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Cirrhosis; FTO; Genetic polymorphisms; Iron metabolism; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; PNPLA3; TM6SF2