The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans.
The MDR1 (ABCB1) gene product P-glycoprotein is a membrane protein, which functions as an ATP-dependent exporter of xenobiotics from cells. Its importance was first recognized because of its role in the development of multidrug resistance (MDR) of cultured tumor cells against various anticancer agents. It is now, however, well established that this transporter is not only expressed in tumor cells, but also in normal tissues with excretory function (intestine, liver, kidney). Since P-glycoprotein has a very broad substrate specificity, it determines disposition of a broad variety of drugs. Moreover, induction and inhibition of P-glycoprotein are new mechanisms for drug interactions in humans. Very recently, systematic screens of the MDR1 gene have identified multiple single nucleotide polymorphisms. Some of those appear to be associated with altered transporter function and expression. This review discusses the currently available data on the influence of MDR1 polymorphisms on P-glycoprotein tissue expression, drug disposition, treatment outcome and disease risk.
Fromm
Martin F
MF
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstr. 112, 70376 Stuttgart, Germany. martin.fromm@ikp-stuttgart.de
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D019450:Genes, MDR / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D011110:Polymorphism, Genetic; D013379:Substrate Specificity; D044465:White People / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1