These authors have equally contributed to this study.
Cirrhosis And Liver Failure
PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis
Article first published online: 19 SEP 2013
© 2013 The Authors. Liver International published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 34, Issue 4, pages 514–520, April 2014
How to Cite
Liver Int. 2014: 34: 514–520
- Issue published online: 10 MAR 2014
- Article first published online: 19 SEP 2013
- Accepted manuscript online: 21 AUG 2013 12:14AM EST
- Manuscript Accepted: 10 AUG 2013
- Manuscript Received: 19 DEC 2012
- Fondazione Onlus Parioli
- Swedish Research Council. Grant Numbers: K2010-55X-11285-13, K2008-65x-20753-01-4, K2013-99X-22230-01-4, 20120533
- Swedish Foundation for Strategic Research
- Age at onset;
- alcohol intake;
- alcoholic liver disease;
- patatin-like phospholipase domain-containing protein 3;
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.
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.
A higher incidence of alcoholic cirrhosis was observed in individuals with an older (≥24 years) compared with a younger (<24) age at onset of at-risk alcohol consumption (P-value < 0.001). Moreover, PNPLA3 148M allele carriers showed an increased incidence of cirrhosis (P-value < 0.001). Both age at onset of at-risk alcohol consumption and PNPLA3 148M allele were independent risk factors for developing cirrhosis (H.R. (95% C.I.): 2.76 (2.18–3.50), P-value < 0.001; 1.53(1.07–2.19), P-value = 0.021 respectively). The 148M allele was associated with a two-fold increased risk of cirrhosis in individuals with a younger compared with an older age at onset of at-risk alcohol consumption (H.R. (95% C.I.): 3.03(1.53–6.00) vs. 1.61(1.09–2.38).
Age at onset of at-risk alcohol consumption and PNPLA3 I148M genetic variant are independently associated with alcoholic cirrhosis incidence.