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Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver

Meier, Yvonne and Pauli-Magnus, Christiane and Zanger, Ulrich M. and Klein, Kathrin and Schaeffeler, Elke and Nussler, Andreas K. and Nussler, Natascha and Eichelbaum, Michel and Meier, Peter J. and Stieger, Bruno. (2006) Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver. Hepatology, Vol. 44, No. 1. pp. 62-74.

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Official URL: http://edoc.unibas.ch/dok/A5261581

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Abstract

Interindividual variability in hepatic canalicular transporter expression might predispose to the development of hepatic disorders such as acquired forms of intrahepatic cholestasis. We therefore investigated expression patterns of bile salt export pump (BSEP, ABCB11), multidrug resistance protein 3 (MDR3, ABCB4), multidrug resistance associated protein 2 (MRP2, ABCC2) and multidrug resistance protein 1 (MDR1, ABCB1) in healthy liver tissue of a white population. Protein expression levels were correlated with specific single nucleotide polymorphisms (SNPs) in the corresponding transporter genes. Hepatic protein expression levels from 110 individuals undergoing liver resection were assessed by Western blot analysis of liver plasma membranes enriched in canalicular marker enzymes. Each individual was genotyped for the following synonymous (s) and nonsynonymous (ns) SNPs: ABCB11: (ns:1457T<C and 2155A<G), ABCB4: (ns:3826A<G) and ABCC2 (ns:1286G<A,3600T<A and 4581G<A) and ABCB1 (ns:2677G<T/A and s:3435C<T). Transporter expression followed unimodal distribution. However, of all tested individuals 30% exhibited a high expression and 32% a low or very low expression phenotype for at least one of the four investigated transport proteins. Transporter expression levels did not correlate with age, sex, underlying liver disease, or presurgery medication. However, low BSEP expression was associated with the 1457C-allele in ABCB11 (P = .167) and high MRP2 expression was significantly correlated with the 3600A and 4581A ABCC2 variants (P = .006). In conclusion, the results demonstrate a considerable interindividual variability of canalicular transporter expression in normal liver. Furthermore, data suggest a polymorphic transporter expression pattern, which might constitute a risk factor for the development of acquired forms of cholestatic liver diseases.
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Saunders
ISSN:0270-9139
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:24
Deposited On:22 Mar 2012 13:37

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