Pharmacogenetics of the Human MDR1 Multidrug Transporter

This review discusses the regulatory role of the human MDR1 multidrug transporter in the traffic of drugs and xenobiotics into the body as well as into certain organs and tissues (e.g. brain, germ cells, fetus). It also explores the relevance of single nucleotide polymorphisms (SNPs) within the MDR1 gene with respect to variations in MDR1 protein expression and function. In silico methods of SNP identification in the MDR1 gene are compared with experimentally determined SNP discovery methods, including direct sequencing and single-strand conformation polymorphism analyses. The distribution of the various SNPs in different ethnic groups is also discussed. We also provide an update on the current status of various association studies that have examined the role of MDR1 SNPs in altering plasma drug concentration, drug-induced side effects, drug response as well as susceptibility to disease, and the potential implications of these findings.