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: Rika Iwata, Katharina Baur, Bruno Stieger, Joachim C Mertens, Ann K Daly, Pascal Frei, Julia Braun, Athanasios Vergopoulos, Felix Stickel, Karim Sabrane, Ina V Martin, Johannes Schmitt, Oliver Goetze, Chris P Day, Beat Müllhaupt, Andreas Geier, Swiss Hepatitis C Cohort Study Group
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 120 Issue 7 Pg. 287-96 (Apr 2011) ISSN: 1470-8736 [Electronic] England
• PMID: 20883210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB11 protein, human
• ATP Binding Cassette Transporter, Subfamily B, Member 11
• ATP-Binding Cassette Transporters
• Bile Acids and Salts

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 11
• ATP-Binding Cassette Transporters (genetics)
• Adult
• Aged
• Aged, 80 and over
• Bile Acids and Salts (blood)
• Disease Progression
• Epidemiologic Methods
• Fatty Liver (blood, genetics)
• Female
• Genetic Predisposition to Disease
• Genotype
• Hepatitis C, Chronic (blood, complications, genetics)
• Humans
• Liver Cirrhosis (blood, genetics, virology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Young Adult