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.