PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis

• Published in: Liver international 2014-04, Vol.34 (4), p.514-520
• Main Authors: Burza, Maria Antonella, Molinaro, Antonio, Attilia, Maria Luisa, Rotondo, Claudia, Attilia, Fabio, Ceccanti, Mauro, Ferri, Flaminia, Maldarelli, Federica, Maffongelli, Angela, De Santis, Adriano, Attili, Adolfo Francesco, Romeo, Stefano, Ginanni Corradini, Stefano
• Format: Article
• Language: English
• Subjects: Adult; Age at onset; Age of Onset; Alcohol Drinking - epidemiology; alcohol intake; alcoholic liver disease; chronic hepatitis-c; Cirrhosis and Liver Failure; damage; fatty liver-disease; fibrosis progression; Gastroenterologi; Gastroenterology and Hepatology; genetics; Genotype; hepatocellular-carcinoma; histological severity; Humans; Incidence; indexes; Italy; Kaplan-Meier Estimate; Linear Models; Lipase - genetics; Liver Cirrhosis, Alcoholic - epidemiology; Liver Cirrhosis, Alcoholic - genetics; Membrane Proteins - genetics; Models, Genetic; Mutation, Missense - genetics; patatin-like phospholipase domain-containing protein; patatin-like phospholipase domain-containing protein 3; polymorphism; Proportional Hazards Models; Retrospective Studies; Risk Factors; susceptibility; transplantation
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.12310

Background & Aims Environmental and genetic factors contribute to alcoholic cirrhosis onset. In particular, age at exposure to liver stressors has been shown to be important in progression to fibrosis in hepatitis C individuals. However, no definite data on the role of age at onset of at‐risk alcohol consumption are available. Moreover, patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) I148M (rs738409) variant has been associated with alcoholic cirrhosis, but only in cross‐sectional studies. The aim of this study was to investigate the role of age at onset of at‐risk alcohol consumption and PNPLA3 I148M variant on alcoholic cirrhosis incidence. Methods A total of 384 at‐risk alcohol drinkers were retrospectively examined. The association among age at onset of at‐risk alcohol consumption, PNPLA3 I148M variant and cirrhosis incidence was tested. Results A higher incidence of alcoholic cirrhosis was observed in individuals with an older (≥24 years) compared with a younger (