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

International Liver Disease Genetics Consortium; Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Berg, Thomas; Dore, Gregory J.; Gr�nb�k, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W.; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; Van Der Poorten, David; George, Jacob; Eslam, Mohammed

Abstract

© 2016 The Author(s). 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.

Citation

International Liver Disease Genetics Consortium, Thabet, K., Asimakopoulos, A., Shojaei, M., Romero-Gomez, M., Mangia, A., …Eslam, M. (2016). MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C. Nature Communications, 7(1), Article 12757. https://doi.org/10.1038/ncomms12757

• Journal Article Type: Article
• Acceptance Date: Jul 29, 2016
• Online Publication Date: Sep 15, 2016
• Publication Date: Sep 15, 2016
• Deposit Date: Oct 20, 2016
• Publicly Available Date: Oct 20, 2016
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 1
• Article Number: 12757
• DOI: https://doi.org/10.1038/ncomms12757
• Keywords: Genetics research; Hepatitis C; Liver fibrosis
• Public URL: https://nottingham-repository.worktribe.com/output/817725
• Publisher URL: http://www.nature.com/articles/ncomms12757
• Contract Date: Oct 20, 2016