Update on nonalcoholic fatty liver disease: genes involved in nonalcoholic fatty liver disease and associated inflammation.
OBJECTIVE
Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases worldwide. Advanced age, extensive overweight and a number of features of the metabolic syndrome are associated with NAFLD severity. The cause of NAFLD is considered multifactorial with a substantial genetic component.


RESULTS
Family members of children with NAFLD demonstrate a higher risk for NAFLD. Whereas such an association only suggests that familial factors are major determinants of whether or not an individual will develop NAFLD, recent genome-wide association studies were able to identify first candidate genes. An allele in patatin-like phospholipase 3, encoding a protein of unknown function with homology to lipid acyl hydrolases, is strongly associated with increased hepatic fat and inflammation. Apolipoprotein C3 gene variants are also associated with NAFLD and insulin resistance. Several other genetic variants have been identified, although with less convincing evidence. These genetic variants involve molecules regulating insulin signaling, lipid metabolism, oxidative stress or fibrogenesis. Furthermore, genetic variants of several cytokines and adipocytokines have been associated with NAFLD.


CONCLUSIONS
Several genetic factors such as patatin-like phospholipase 3 or apolipoprotein C3 have been recently characterized in NAFLD. Further studies to identify their interaction with environmental factors are eagerly warranted.
Tilg
Herbert
H
Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Innsbruck, Austria. Herbert.Tilg@i-med.ac.at
Moschen
Alexander
A
D053305:Apolipoprotein C-III / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D005234:Fatty Liver / Q000150:complications / Q000235:genetics*; D005355:Fibrosis / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D007328:Insulin / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D009765:Obesity / Q000150:complications / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics; D010740:Phospholipases / Q000235:genetics*
D053305:Apolipoprotein C-III; D016207:Cytokines; D005819:Genetic Markers; D007328:Insulin; D006867:Hydrolases; D010740:Phospholipases