title: The membrane-bound O-acyltransferase domain-containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B.
abstract: Chronic hepatitis B (CHB) is characterized by hepatic inflammation that promotes progression to cirrhosis and predisposes to the development of hepatocellular carcinoma (HCC). Subtle interindividual genetic variation as well as viral and environmental factors interact to determine disease progression between individuals. Recently, the rs641738 membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) polymorphism was demonstrated to influence histological liver damage in alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C, but no data are available for CHB. We evaluated rs641738 influence on disease severity in a cohort of 1,101 patients with CHB. Forty-two patients underwent gene expression analysis to assess the functional consequences of rs641738 on hepatic MBOAT7 expression. The minor allele (T) of rs641738 was associated with greater inflammation (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06-1.95; P = 0.001) and fibrosis (OR = 1.31; 95% CI, 1.19-1.92; P = 0.01). Risk allele frequency in whites (0.43) was greater than in Chinese (0.24), translating to a larger size effect in the former. The rs641738 (T) allele was associated with lower hepatic MBOAT7 expression (P = 0.008), and the latter was associated with serum liver enzymes and inflammation. Neither patatin-like phospholipase domain-containing protein 3 rs738409 nor transmembrane 6 superfamily member 2 rs58542926 polymorphisms influenced disease severity.
  
  
  
  In patients with CHB, MBOAT7 rs641738 influences hepatic inflammation and fibrosis stage. (Hepatology 2017;65:1840-1850).
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.|Biochemistry Department, Faculty of Pharmacy, Minia University, Minia, Egypt.
authors.forename: Khaled
authors.initials: K
authors.lastname: Thabet
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease and State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong.
authors.forename: Henry Lik Yuen
authors.initials: HLY
authors.lastname: Chan
authors.affiliation: Sezione di Gastroenterologia, DiBiMIS, University of Palermo, Palermo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.affiliation: Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Andre
authors.initials: A
authors.lastname: Boonstra
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Willem P
authors.identifier: 0000-0001-8713-1481
authors.initials: WP
authors.lastname: Brouwer
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy.
authors.forename: Maria Lorena
authors.initials: ML
authors.lastname: Abate
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease and State Key Laboratory of Digestive Disease, the Chinese University of Hong Kong.
authors.forename: Vincent Wai-Sun
authors.initials: VW
authors.lastname: Wong
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Minia University, Minia, Egypt.
authors.forename: Maiiada
authors.initials: M
authors.lastname: Nazmy
authors.affiliation: Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany.
authors.forename: Janett
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, NSW, Australia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Eslam
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D000217:Acyltransferases / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D015331:Cohort Studies; D016001:Confidence Intervals; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D008565:Membrane Proteins; D000217:Acyltransferases; C000616532:MBOAT7 protein, human; D000123:Acetyltransferases