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PNPLA3 genetic variation in alcoholic steatosis and liver disease progression


Stickel, Felix; Hampe, Jochen; Trépo, Eric; Datz, Christian; Romeo, Stefano (2015). PNPLA3 genetic variation in alcoholic steatosis and liver disease progression. Hepatobiliary surgery and nutrition, 4(3):152-160.

Abstract

Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3's function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients.

Abstract

Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3's function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:June 2015
Deposited On:23 Jul 2015 08:12
Last Modified:05 Apr 2016 19:18
Publisher:AME Publishing Company
ISSN:2304-3881
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.3978/j.issn.2304-3881.2014.11.04
Official URL:http://www.thehbsn.org/article/view/5260/6094
PubMed ID:26151055

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