title: MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C.
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.
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.|Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 6111, Egypt.
authors.forename: Khaled
authors.initials: K
authors.lastname: Thabet
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Asimakopoulos
authors.affiliation: Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, Sydney, New South Wales 2145, Australia.|Nepean Genomic Research Group, ICU, Nepean Hospital, Kingswood, New South Wales 2747, Australia.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shojaei
authors.affiliation: Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, 41014 Sevilla, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.affiliation: Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, 71013 San Giovanni Rotondo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: William L
authors.initials: WL
authors.lastname: Irving
authors.affiliation: Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, 04103 Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: Kirby Institute, The University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK-8000 Aarhus, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbæk
authors.affiliation: Institute of Translational and Stratified Medicine, Plymouth University, Plymouth PL4 8AA, UK.
authors.forename: David
authors.initials: D
authors.lastname: Sheridan
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, 10126 Turin, Italy.
authors.forename: Maria Lorena
authors.initials: ML
authors.lastname: Abate
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, 10126 Turin, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.affiliation: Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney, New South Wales 2747, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Weltman
authors.affiliation: Department of Gastroenterology and Hepatology, Fremantle Hospital, Fremantle, Western Australia 6160, Australia.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Mollison
authors.affiliation: Department of Gastroenterology and Hepatology, Royal Perth Hospital, Western Australia 6000, Australia.
authors.forename: Wendy
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Gastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, New South Wales 2031, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Riordan
authors.affiliation: Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, 04103 Leipzig, Germany.
authors.forename: Janett
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Department of Internal Medicine I, University of Bonn, 53105 Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.affiliation: Department of Internal Medicine I, University of Bonn, 53105 Bonn, Germany.
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 6111, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Wahid
authors.affiliation: Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, 41014 Sevilla, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Rojas
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
authors.forename: Rose
authors.initials: R
authors.lastname: White
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.|Centre for Infectious Diseases and Microbiology, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney at Westmead Hospital, Westmead, New South Wales 2145, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Douglas
authors.affiliation: Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, New South Wales 2145, Australia.
authors.forename: Duncan
authors.initials: D
authors.lastname: McLeod
authors.affiliation: Princess Alexandra Hospital, School of Medicine, The University of Queensland, Woolloongabba, Queensland 4102, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Powell
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
authors.forename: David
authors.initials: D
authors.lastname: van der Poorten
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Eslam
mesh_terms: D000217:Acyltransferases / Q000097:blood / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000235:genetics; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics*; D006801:Humans; D007107:Immune System / Q000378:metabolism; D008103:Liver Cirrhosis / Q000235:genetics* / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000821:virology; D008262:Macrophage Activation; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide
chemical_list: D008565:Membrane Proteins; D000217:Acyltransferases; C000616532:MBOAT7 protein, human