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...

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Vydané v:	Nature genetics Ročník 40; číslo 12; s. 1461 - 1465
Hlavní autori:	Romeo, Stefano, Kozlitina, Julia, Xing, Chao, Pertsemlidis, Alexander, Cox, David, Pennacchio, Len A, Boerwinkle, Eric, Cohen, Jonathan C, Hobbs, Helen H
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.12.2008 Nature Publishing Group
Predmet:	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
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Shrnutí:	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.
Bibliografia:	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