Variant in PNPLA3 is associated with alcoholic liver disease.

Nature genetics ·Vol. 42 ·No. 1 ·2010-01-00 ·Pages 21-3

Tian C, Stokowski RP, Kershenobich D, Ballinger DG, Hinds DA

Abstract

Two genome-wide association studies (GWAS) have described associations of variants in PNPLA3 with nonalcoholic fatty liver and plasma liver enzyme levels. We investigated the contributions of these variants to liver disease in Mestizo subjects with a history of alcohol dependence. We found that rs738409 in PNPLA3 is strongly associated with alcoholic liver disease and clinically evident alcoholic cirrhosis (unadjusted OR= 2.25, P=1.7 x 10(-10); ancestry-adjusted OR=1.79, P=1.9 x 10(-5)).

MeSH Terms

Adult Female Gene Frequency Genetic Predisposition to Disease Genetic Variation Genotype Humans Lipase/genetics Liver Cirrhosis, Alcoholic/genetics Liver Diseases, Alcoholic/genetics Logistic Models Male Membrane Proteins/genetics Middle Aged Polymorphism, Single Nucleotide

Chemicals

Membrane Proteins Lipase adiponutrin, human

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Tian Chao

Perlegen Sciences, Mountain View, California, USA.

Stokowski Renee P

Kershenobich David

Ballinger Dennis G

Hinds David A

References (12)

12 references, click to expand

Risk factors for chronic liver disease in Blacks, Mexican Americans, and Whites in the United States: results from NHANES IV, 1999-2004.
Am J Gastroenterol. 2008 Sep;103(9):2231-8 PMID: 18671818
Matching strategies for genetic association studies in structured populations.
Am J Hum Genet. 2004 Feb;74(2):317-25 PMID: 14740319
A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans.
Diabetologia. 2009 Jun;52(6):1056-60 PMID: 19224197
Transection of the oesophagus for bleeding oesophageal varices.
Br J Surg. 1973 Aug;60(8):646-9 PMID: 4541913
Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities.
J Biol Chem. 2004 Nov 19;279(47):48968-75 PMID: 15364929
Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.
Am J Hum Genet. 2008 Oct;83(4):520-8 PMID: 18940312
Alcohol and lipid metabolism.
Am J Physiol Endocrinol Metab. 2008 Jul;295(1):E10-6 PMID: 18349117
A genomewide single-nucleotide-polymorphism panel for Mexican American admixture mapping.
Am J Hum Genet. 2007 Jun;80(6):1014-23 PMID: 17557415
A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C.
Hepatology. 2007 Aug;46(2):297-306 PMID: 17461418
Adiponutrin, a transmembrane protein corresponding to a novel dietary- and obesity-linked mRNA specifically expressed in the adipose lineage.
J Biol Chem. 2001 Sep 7;276(36):33336-44 PMID: 11431482
Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease.
Nat Genet. 2008 Dec;40(12):1461-5 PMID: 18820647
The epidemiology of alcoholic liver disease.
Alcohol Res Health. 2003;27(3):209-19 PMID: 15535449

Article Info

Journal

Nature genetics

Abbr.

Nat Genet

ISSN

1546-1718

DOI

10.1038/ng.488

Published

2010-01-00

Epub

2009-00-29

Pages

21-3

Language

English

Region

United States

NLM ID

9216904

Subset

Corrections

CommentIn

PMID: 20373372

External Links

PubMed source DOI: 10.1038/ng.488 View journal details

Analysis Services

Variant in PNPLA3 is associated with alcoholic liver disease.

Contact

WeChat Official Account