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

• Published in: Nature communications Vol. 7; no. 1; p. 12757
• Main Authors: Thabet, Khaled, Asimakopoulos, Anastasia, Shojaei, Maryam, Romero-Gomez, Manuel, Mangia, Alessandra, Irving, William L., Berg, Thomas, Dore, Gregory J., Grønbæk, 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.09.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308/2056; 692/4020/4021/1607/1605; 692/4020/4021/234/2513/1551; Acyltransferases - blood; Acyltransferases - genetics; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; Case-Control Studies; Cohort Studies; Disease Progression; Enzymes; Fatty Liver - genetics; Female; Gastroenterology; Genomes; Genotype & phenotype; Hepatitis C; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - genetics; Hepatology; Hospitals; Humanities and Social Sciences; Humans; Immune System - metabolism; Infectious diseases; Liver cirrhosis; Liver Cirrhosis - genetics; Liver Cirrhosis - virology; Liver diseases; Liver Neoplasms - genetics; Liver Neoplasms - virology; Macrophage Activation; Male; Medical research; Membrane Proteins - blood; Membrane Proteins - genetics; Middle Aged; multidisciplinary; Oxidative Stress; Polymorphism; Polymorphism, Single Nucleotide; Science; Science (multidisciplinary); Viral infections; White people; United Kingdom > UK; Denmark; Italy; Australia; Western Australia Australia; Aarhus Denmark; Germany; New South Wales Australia
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12757

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. Chronic Hepatitis C infection is associated with a broad spectrum of liver pathologies, ranging from inflammation to fibrosis and liver cancer. Here Thabet et al . identified a polymorphism in the gene MBOAT7 that is associated with increased hepatic inflammation and higher risk of fibrosis development and progression.