Dataset Information

MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C?>?T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08-2.55; n?=?765), particularly in those without advanced fibrosis (p?

SUBMITTER: Donati B

PROVIDER: S-EPMC5495751 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals.

Donati Benedetta B Dongiovanni Paola P Romeo Stefano S Meroni Marica M McCain Misti M Miele Luca L Petta Salvatore S Maier Silvia S Rosso Chiara C De Luca Laura L Vanni Ester E Grimaudo Stefania S Romagnoli Renato R Colli Fabio F Ferri Flaminia F Mancina Rosellina Margherita RM Iruzubieta Paula P Craxi Antonio A Fracanzani Anna Ludovica AL Grieco Antonio A Corradini Stefano Ginanni SG Aghemo Alessio A Colombo Massimo M Soardo Giorgio G Bugianesi Elisabetta E Reeves Helen H Anstee Quentin M QM Fargion Silvia S Valenti Luca L

Scientific reports 20170703 1

Nonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C > T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08-2.55; n = 765), particularly in those without advanced fibrosis (p < 0.001). The risk T allele was linked to 3'-UTR variation in MBOAT ...[more]

PMID: 28674415

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Project description:Background & aimsNonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene (MBOAT7, also called LPIAT1) and transmembrane channel-like 4 gene (TMC4) increased the risk for cirrhosis in alcohol abusers. We investigated whether the MBOAT7-TMC4 is a susceptibility locus for the development and progression of NAFLD.MethodsWe genotyped rs641738 in DNA collected from 3854 participants from the Dallas Heart Study (a multi-ethnic population-based probability sample of Dallas County residents) and 1149 European individuals from the Liver Biopsy Cross-Sectional Cohort. Clinical and anthropometric data were collected, and biochemical and lipidomics were measured in plasma samples from participants. A total of 2736 participants from the Dallas Heart Study also underwent proton magnetic resonance spectroscopy to measure hepatic triglyceride content. In the Liver Biopsy Cross-Sectional Cohort, a total of 1149 individuals underwent liver biopsy to diagnose liver disease and disease severity.ResultsThe genotype rs641738 at the MBOAT7-TMC4 locus associated with increased hepatic fat content in the 2 cohorts, and with more severe liver damage and increased risk of fibrosis compared with subjects without the variant. MBOAT7, but not TMC4, was found to be highly expressed in the liver. The MBOAT7 rs641738 T allele was associated with lower protein expression in the liver and changes in plasma phosphatidylinositol species consistent with decreased MBOAT7 function.ConclusionsWe provide evidence for an association between the MBOAT7 rs641738 variant and the development and severity of NAFLD in individuals of European descent. This association seems to be mediated by changes in the hepatic phosphatidylinositol acyl-chain remodeling.

Dataset Information

MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals.

Publications

MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals.

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