Placental P-glycoprotein and breast cancer resistance protein: influence of polymorphisms on fetal drug exposure and physiology

Abstract

Recent studies have illustrated the importance of placental drug transport proteins, such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) in limiting fetal exposure to drugs and toxins. Moreover, increasing evidence supports a role for Pgp and BCRP in the normal development and physiological function of the placenta. Several single nucleotide polymorphisms (SNPs) in the genes encoding Pgp and BCRP have been described and are associated with altered protein expression, transporter activity, and clinical outcome in studies focusing on tissues other than the placenta. This review aims to summarize current research regarding the association between these polymorphisms and expression and function in the placenta. The influence of these genotypes on fetal drug exposure and altered placental physiology or development is also presented. To date, evidence suggests that SNPs in both ABCB1 and ABCG1 can alter expression of their respective protein; however, the functional significance of these polymorphisms is less clear. An understanding of this genotype-phenotype relationship will allow for prediction of susceptible or favorable genotypes in order to personalize medication choices to minimize fetal exposure to teratogens, or to maximize pharmacological therapy to the fetus.