Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

Helen Hobbs and colleagues report an association between coding variation in PNPLA3 and susceptibility to nonalcoholic fatty liver disease. The associated alleles vary in frequency among Hispanics, African Americans and European Americans and contribute to differences in disease prevalence among the...

Full description

Saved in:
Bibliographic Details
Published in:Nature genetics Vol. 40; no. 12; pp. 1461 - 1465
Main Authors: Romeo, Stefano, Kozlitina, Julia, Xing, Chao, Pertsemlidis, Alexander, Cox, David, Pennacchio, Len A, Boerwinkle, Eric, Cohen, Jonathan C, Hobbs, Helen H
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.12.2008
Nature Publishing Group
Subjects:
African Americans
Agriculture
Animal Genetics and Genomics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
Diet
Fatty liver
Fatty Liver - epidemiology
Fatty Liver - ethnology
Fatty Liver - genetics
Female
Fundamental and applied biological sciences. Psychology
Gastroenterology. Liver. Pancreas. Abdomen
Gene Function
Genetic aspects
Genetic diversity
Genetic Predisposition to Disease
Genetic susceptibility
Genetic variance
Genetic Variation
Genetics of eukaryotes. Biological and molecular evolution
Hispanic people
Human Genetics
Humans
letter
Lipase - genetics
Liver diseases
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Membrane Proteins - genetics
Other diseases. Semiology
Plasma
Risk factors
Single nucleotide polymorphisms
United States
Digestive diseases
Hepatic disease
Genetic variability
Non alcoholic steatohepatitis
Genetic variant
ISSN:1061-4036, 1546-1718, 1546-1718
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Helen Hobbs and colleagues report an association between coding variation in PNPLA3 and susceptibility to nonalcoholic fatty liver disease. The associated alleles vary in frequency among Hispanics, African Americans and European Americans and contribute to differences in disease prevalence among these ancestry groups. Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ancestry groups. To identify genetic variants contributing to differences in hepatic fat content, we carried out a genome-wide association scan of nonsynonymous sequence variations ( n = 9,229) in a population comprising Hispanic, African American and European American individuals. An allele in PNPLA3 (rs738409[G], encoding I148M) was strongly associated with increased hepatic fat levels ( P = 5.9 × 10 −10 ) and with hepatic inflammation ( P = 3.7 × 10 −4 ). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was more than twofold higher in PNPLA3 rs738409[G] homozygotes than in noncarriers. Resequencing revealed another allele of PNPLA3 (rs6006460[T], encoding S453I) that was associated with lower hepatic fat content in African Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ancestry-related and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
USDOE Office of Science (SC), Biological and Environmental Research (BER)
These authors contributed equally to this work.
ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/ng.257