title: PNPLA3 I148M variant and hepatocellular carcinoma: a common genetic variant for a rare disease.
abstract: Hepatocellular carcinoma (HCC) is highly associated with chronic liver disease. The rs738409 genetic variant in the patatin-like phospholipase domain-containing 3 (PNPLA3, adiponutrin) gene has been implicated as a genetic determinant of the entire spectrum of liver diseases, ranging from steatosis, chronic hepatitis, cirrhosis and ultimately to HCC. In this review, first we will examine the current genetic theories of disease susceptibility. Next, we will analyze the evidences for the association between PNPLA3 I148M variant and HCC. Moreover, we will exploit this association to propose a new paradigm in human genetics: a common genetic variant contributing to a rare disease. Finally, we will examine the molecular genetics of PNPLA3 and, specifically, the theories that have been proposed to explain the function of PNPLA3 in health and disease.
authors: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Section of Internal Medicine, Italy. luca.valenti@unimi.it
authors: Luca
authors: L
authors: Valenti
authors: Paola
authors: P
authors: Dongiovanni
authors: Stefano
authors: S
authors: Ginanni Corradini
authors: Maria Antonella
authors: MA
authors: Burza
authors: Stefano
authors: S
authors: Romeo
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D005819:Genetic Markers / Q000235:genetics*; D006521:Hepatitis, Chronic / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D035583:Rare Diseases; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D005819:Genetic Markers; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Hepatocellular carcinoma; Human genetics; Patatin-like phospholipase domain containing 3