title: A common polymorphism in the ABCB11 gene is associated with advanced fibrosis in hepatitis C but not in non-alcoholic fatty liver disease.
abstract: Chronic HCV (hepatitis C virus)-associated cirrhosis represents a major indication for liver transplantation. Bile acids contribute to hepatic stellate cell activation as a key event in fibrogenesis. The aim of the present study was to investigate the role of bile acids and polymorphisms in bile acid level-regulating genes on fibrosis progression. A total of 206 subjects with chronic HCV infection were included for ABCB11 (ATP-binding cassette, subfamily B, member II) 1331T>C and NR1H4 (nuclear receptor) -1G>T genotyping, 178 of which were analysed for fibrosis stage. Exclusion criteria were HBV (hepatitis B virus) or HIV coinfection, alcohol >40 g/day and morbid obesity. A total of 358 patients with NAFLD (non-alcoholic fatty liver disease) were genotyped for comparison with a non-viral liver disease. Caucasian individuals (n = 110), undergoing liver resection for focal hepatic metastasis, served as controls. The ABCB11 1331C allele was significantly overrepresented in HCV patients compared with controls {allelic frequency 62.9%; OR (odds ratio), 1.41 [95% CI (confidence interval), 1.012-1.965]}. Median plasma bile acid levels were not significantly increased in the CC compared with TT genotype [7.2 (1-110) μmol/l compared with 3.5 (1-61) μmol/l; values are medians (range). A significant association between the presence of cirrhosis and ABCB11 genotype (CC compared with CT or TT, P=0.047) was observed in the χ2 test and independent of other risk factors of age, gender, body mass index and disease duration in multivariate analysis (P = 0.010). No such association could be observed in fatty liver patients with regard to advanced fibrosis (F ≥ 2). The common ABCB11 1331CC genotype, which is present in 40% of HCV patients and renders the carrier susceptible to increased bile acid levels, is associated with cirrhosis.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, University Hospital Zurich (USZ), CH-8091 Zurich, Switzerland.
authors.forename: Rika
authors.initials: R
authors.lastname: Iwata
authors.forename: Katharina
authors.initials: K
authors.lastname: Baur
authors.forename: Bruno
authors.initials: B
authors.lastname: Stieger
authors.forename: Joachim C
authors.initials: JC
authors.lastname: Mertens
authors.forename: Ann K
authors.initials: AK
authors.lastname: Daly
authors.forename: Pascal
authors.initials: P
authors.lastname: Frei
authors.forename: Julia
authors.initials: J
authors.lastname: Braun
authors.forename: Athanasios
authors.initials: A
authors.lastname: Vergopoulos
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Karim
authors.initials: K
authors.lastname: Sabrane
authors.forename: Ina V
authors.initials: IV
authors.lastname: Martin
authors.forename: Johannes
authors.initials: J
authors.lastname: Schmitt
authors.forename: Oliver
authors.initials: O
authors.lastname: Goetze
authors.forename: Chris P
authors.initials: CP
authors.lastname: Day
authors.forename: Beat
authors.initials: B
authors.lastname: Müllhaupt
authors.forename: Andreas
authors.initials: A
authors.lastname: Geier
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001647:Bile Acids and Salts / Q000097:blood; D018450:Disease Progression; D004812:Epidemiologic Methods; D005234:Fatty Liver / Q000097:blood / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts