A frequent variant in the human bile salt export pump gene ABCB11 is associated with hepatitis C virus infection, but not liver stiffness in a German population

BMC Gastroenterol. 2012 Jun 8:12:63. doi: 10.1186/1471-230X-12-63.

Abstract

Background: The human ATP-binding cassette, subfamily B, member 11 (ABCB11) gene encodes the bile salt export pump, which is exclusively expressed at the canalicular membrane of hepatocytes. A frequent variant in the coding region, c.1331 T>C, leading to the amino acid exchange p.V444A, has been associated with altered serum bile salt levels in healthy individuals and predisposes homozygous carriers of the [C] allele for obstetric cholestasis. Recently, elevated bile salt levels were shown to be significantly associated with rates and risk of cirrhosis in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon-α2 and ribavirin, suggesting a potential role for bile salt levels in HCV treatment outcomes and in the fibrogenic evolution of HCV-related liver disease. The aim of this study was to investigate a possible association of ABCB11 c.1331 T>C with hepatitis C virus (HCV) infection and fibrosis stages as assessed by non-invasive transient elastography in a German cohort of patients.

Methods: ABCB11 c.1331 T>C genotype was determined by allelic discrimination assay in 649 HCV infected cases and 413 controls. Overall, 444 cases were staged for fibrotic progression by measurement of liver stiffness.

Results: Homo- or heterozygous presence of the frequent [C] allele was associated with HCV positivity (OR = 1.41, CI = 1.02 - 1.95, p = 0.037). No association was detectable between the ABCB11 c.1331 T>C genotype and increased liver stiffness.

Conclusions: Our data confirm that homozygous presence of the major [C] allele of ABCB11 c.1331 T>C is a genetic susceptibility factor for HCV infection, but not for liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Disease Progression
  • Elasticity
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Germany / epidemiology
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Young Adult

Substances

  • ABCB11 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • ATP-Binding Cassette Transporters