Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

✍ Scribed by Romeo, Stefano (author);Kozlitina, Julia (author);Xing, Chao (author);Pertsemlidis, Alexander (author);Cox, David (author);Pennacchio, Len A. (author);Boerwinkle, Eric (author);Cohen, Jonathan C. (author);Hobbs, Helen H. (author)

• Book ID: 109914348
• Publisher: Nature Publishing Group
• Year: 2008
• Tongue: English
• Weight: 491 KB
• Volume: 40
• Category: Article
• ISSN: 1061-4036
• DOI: 10.1038/ng.257

✦ Synopsis

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.