The genetics of NAFLD.
NAFLD is a disease spectrum ranging from simple steatosis, through steatohepatitis to fibrosis and, ultimately, cirrhosis. This condition is characterized by considerable interpatient variability in terms of severity and rate of progression: although a substantial proportion of the population is at risk of progressive disease, only a minority experience associated morbidity. As such, NAFLD is best considered a complex disease trait resulting from environmental exposures acting on a susceptible polygenic background and comprising multiple independent modifiers. Much ongoing research is focused on identifying the genetic factors that contribute to NAFLD pathogenesis. This Review describes the current status of the field, discussing specific genetic and epigenetic modifiers, including the mechanisms through which genes identified by genome-wide association studies, including PNPLA3, influence disease progression.
Liver Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, 4th Floor, William Leech Building, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK.
Quentin M
QM
Anstee
Christopher P
CP
Day
D018450:Disease Progression; D057890:Epigenomics; D005234:Fatty Liver / Q000235:genetics* / Q000503:physiopathology; D055106:Genome-Wide Association Study; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D065626:Non-alcoholic Fatty Liver Disease; D012720:Severity of Illness Index; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent