MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

Thabet, Khaled and Asimakopoulos, Anastasia and Shojaei, Maryam and Romero-Gomez, Manuel and Mangia, Alessandra and Irving, William L. and Berg, Thomas and Dore, Gregory J. and Grønbæk, Henning and Sheridan, David and Abate, Maria Lorena and Bugianesi, Elisabetta and Weltman, Martin and Mollison, Lindsay and Cheng, Wendy and Riordan, Stephen and Fischer, Janett and Spengler, Ulrich and Nattermann, Jacob and Wahid, Ahmed and Rojas, Angela and White, Rose and Douglas, Mark W. and McLeod, Duncan and Powell, Elizabeth and Liddle, Christopher and van der Poorten, David and George, Jacob and Eslam, Mohammed and Gallego-Duran, Rocio and Applegate, Tanya and Bassendine, Margaret and Rosso, Chiara and Mezzabotta, Lavinia and Leung, Reynold and Malik, Barbara and Matthews, Gail and Grebely, Jason and Fragomeli, Vincenzo and Jonsson, Julie R. and Santaro, Rosanna (2016) MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C. Nature Communications, 7 . 12757/1-12757/10. ISSN 2041-1723

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Abstract

Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis.

Item Type: Article
Keywords: Genetics research; Hepatitis C; Liver fibrosis
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.1038/ncomms12757
Depositing User: Eprints, Support
Date Deposited: 20 Oct 2016 08:49
Last Modified: 18 Oct 2017 18:59
URI: http://eprints.nottingham.ac.uk/id/eprint/37769

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