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Pharmacogenetics of hepatocellular transporters

Pauli-Magnus, Christiane and Meier, Peter J.. (2003) Pharmacogenetics of hepatocellular transporters. Pharmacogenetics, Vol. 13, H. 4. pp. 189-198.

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Official URL: http://edoc.unibas.ch/dok/A5261620

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Abstract

One of the main functions of the liver is the production of bile and the biliary secretion of endogenous and exogenous substances, including drugs and drug metabolites. Bile formation is a complex sequence of cellular events, which involves uptake of bile constituents and xenobiotics on the basolateral (sinusoidal) plasma membrane of hepatocytes and secretion of cholephilic compounds across the apical (canalicular) membrane. These uptake and efflux processes are maintained by distinct transport systems expressed at the two polar surface domains of liver cells. Any functional disturbance of these canalicular transport systems can lead to cholestatic liver disease, which is associated with intracellular accumulation of toxic bile constituents and consecutive cholestatic liver cell damage. Interaction of drugs with hepatobiliary transport systems is increasingly recognized as cause of acquired cholestatic syndromes. Thereby, genetically determined alterations of hepatobiliary transporter functions are important risk factors for an individual's susceptibility to develop cholestasis. Especially, mutations in canalicular transporter genes can cause certain forms of hereditary cholestatic liver disease, including progressive familial intrahepatic cholestasis or intrahepatic cholestasis of pregnancy. In addition, systematic genetic screenings have discovered numerous single nucleotide polymorphisms in hepatobiliary transporter genes that lead to amino acid exchanges in the encoded proteins. However, the functional consequences and the clinical relevance of most of these polymorphisms remain to be defined. This overview summarizes the physiological function of human hepatobiliary transport systems and discusses the impact of their genetic variations for the pathophysiology of cholestatic syndromes and the pharmacogenetics of drug-induced cholestasis.
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:Lippincott Williams & Wilkins
ISSN:0960-314X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:27
Deposited On:22 Mar 2012 13:58

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