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.
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.
Department of Medicine II, Saarland University Medical Center, Homburg, Germany. roman.muellenbach@uks.eu
Roman
R
Müllenbach
Susanne N
SN
Weber
Marcin
M
Krawczyk
Vincent
V
Zimmer
Christoph
C
Sarrazin
Frank
F
Lammert
Frank
F
Grünhage
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; D018450:Disease Progression; D004548:Elasticity; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005858:Germany / Q000453:epidemiology; D019698:Hepatitis C, Chronic / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters