Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis.
Liver fat accumulation generally related to systemic insulin resistance characterizes nonalcoholic fatty liver disease (NAFLD), which in the presence of nonalcoholic steatohepatitis (NASH) can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease in Western countries. Epidemiological, familial, and twin studies provide evidence for a strong genetic component of NAFLD susceptibility. Recently, genome-wide association studies led to the identification of the major inherited determinants of hepatic fat accumulation: patatin-like phospholipase domain-containing 3 (PNPLA3) I148M gene and transmembrane 6 superfamily member 2 (TM6SF2) E167K gene variants, involved in lipid droplets remodelling and very low-density lipoproteins secretion, are the major determinants of interindividual differences in liver steatosis, and susceptibility to progressive NASH. In this review, we aimed to provide an overview of recent insights into the genetics of hepatic fat accumulation and steatohepatitis.
Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy.
Paola
P
Dongiovanni
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 3, 40530 Gothenburg, Sweden ; Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Viale Europa, 88100 Catanzaro, Italy.
Stefano
S
Romeo
Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy ; Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy.
Luca
L
Valenti
D000818:Animals; D005223:Fats / Q000378:metabolism*; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
D005223:Fats; D008079:Lipoproteins, VLDL