Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance

Details

Serval ID
serval:BIB_111D08D8358F
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance
Journal
Clinical Pharmacology and Therapeutics
Author(s)
Marzolini  Catia, Paus  Erik, Buclin  Thierry, Kim  Richard B.
ISSN
0009-9236
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
75
Number
1
Pages
13-33
Notes
SAPHIRID:62204
Abstract
Drug transporters are increasingly recognized to be important to drug disposition and response.
P-glycoprotein, the encoded product of the human MDR1 (ABCB1) gene, is of particular clinical relevance in
that this transporter has broad substrate specificity, including a variety of structurally divergent drugs in
clinical use today. Moreover, expression of this efflux transporter in certain tissue compartments such as the
gastrointestinal tract and brain capillary endothelial cells limits oral absorption and central nervous system
entry of many drugs. Recently, a number of single-nucleotide polymorphisms (SNPs) in MDR1 have been
identified. An increasing number of studies have also implicated certain commonly occurring SNPs in MDR1
in problems including altered drug levels and host susceptibility to diseases such as Parkinson's disease,
inflammatory bowel disease, refractory seizures, and CD4 cell recovery during human immunodeficiency
virus therapy. However, in many such cases, the reported effects of MDR1 SNPs have been inconsistent and,
in some cases, conflicting. In this review SNPs in MDR1 in relation to population frequencies, drug levels, and
phenotypes are outlined. In addition, issues relating to MDR1 haplotypes, environmental factors, and study
design, as potential confounding factors of the observed MDR1 polymorphism effect in vivo, are also
discussed.
Pubmed
Web of science
Create date
05/02/2008 13:38
Last modification date
20/08/2019 12:38
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