S25 Genetic Regulation of Drug Transporters

Lauren M. Aleksunes , Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ
Interindividual differences in drug efficacy and toxicity are controlled by multiple pathways involved in cellular signaling, metabolism, and transport. Genetic variants in uptake and efflux drug transporters are gaining increasing attention for their ability to influence pharmacokinetics and adverse events. In particular, single nucleotide polymorphisms (SNPs) in coding and non-coding regions of transporter genes and their regulatory regions can influence mRNA and protein stability and turnover, trafficking and localization, as well as transport activity. This presentation will describe the impact of transporter genetic variants on drug and chemical responses in vitro and in clinical practice. In particular, we will explore the influence of coding and non-coding ABCG2 genetic variants on BCRP mRNA and protein expression in healthy, term placentas from a diverse U.S. patient population. The influence of the C421A/Q141K ABCG2 variant on the expression of placental BCRP protein will be discussed along with in vitro transport studies of environmental and dietary chemicals. Collectively, these studies provide novel insight into the genetic variability of transporters in the blood-placental barrier and fetal protection from xenobiotic exposure.