Variant adiponutrin (PNPLA3) represents a common fibrosis risk gene: non-invasive elastography-based study in chronic liver disease.

Abstract

BACKGROUND & AIMS:

Recent genome-wide association studies have identified the variant p.I148M of the adiponutrin gene PNPLA3 as a risk factor for developing severe forms of non-alcoholic and alcoholic liver diseases. The risk allele confers an increased risk for fatty liver disease and elevated serum aminotransferase activities reflecting liver injury. In the current elastography-based study, we investigate variant adiponutrin as genetic determinant of liver fibrosis, the hallmark of all chronic liver diseases.

METHODS:

In this observational cross-sectional study, we staged 899 patients with different chronic liver diseases non-invasively by transient elastography (Fibroscan) and genotyped them for variant adiponutrin (rs738409) by PCR-based assays. A subgroup of 229 patients consented to percutaneous liver biopsy, validating the accuracy of elastography in staging fibrosis (ρ=0.743, p<0.01).

RESULTS:

Carriers of distinct p.I148M adiponutrin genotypes display significant (p=0.017) differences in liver stiffness determined by elastography. In particular, individuals carrying the allele [G] are at higher risk of developing liver cirrhosis defined by stiffness values ≥13.0kPa (OR=1.56, p=0.005). Of note, the PNPLA3 risk variant advances fibrosis in the total cohort as well as in the subgroups of patients with viral hepatitis and non-viral liver diseases and contributes 16% of the total cirrhosis risk.

CONCLUSIONS:

The adiponutrin risk variant is a common genetic determinant of progressive liver fibrosis. Our results underpin non-invasive follow-up for individuals with chronic liver disease at-risk for developing advanced fibrosis and cirrhosis.

• Authors: Marcin Krawczyk, Frank Grünhage, Vincent Zimmer, Frank Lammert
• Journal: Journal of hepatology (J Hepatol) Vol. 55 Issue 2 Pg. 299-306 (Aug 2011) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 21168459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• DNA Primers
• Membrane Proteins
• Lipase
• adiponutrin, human

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Base Sequence
• Chronic Disease
• Cross-Sectional Studies
• DNA Primers (genetics)
• Elasticity Imaging Techniques
• Female
• Genetic Predisposition to Disease
• Humans
• Lipase (genetics)
• Liver Cirrhosis (genetics, pathology)
• Liver Diseases (genetics, pathology)
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk Factors
• Young Adult