Pharmacogenetics of membrane transporters: a review of current approaches

Methods Mol Biol. 2014:1175:91-120. doi: 10.1007/978-1-4939-0956-8_6.

Abstract

This chapter provides a review of the pharmacogenetics of membrane transporters, including ABC transporters and OATPs. Membrane transporters are heavily involved in drug disposition, by actively transporting substrate drugs between organs and tissues. As such, polymorphisms in the genes encoding these proteins may have a significant effect on the absorption, distribution, metabolism, excretion, and activity of compounds. Although few drug transporter polymorphisms have transitioned from the bench to the bedside, this chapter discusses clinical development of transporter pharmacogenetic markers. Finally, development of SLCO1B1 genotyping to avoid statin induced adverse drug reactions is discussed as a model case for transporter pharmacogenetics clinical development.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug-Related Side Effects and Adverse Reactions / genetics
  • Genetic Variation
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Liver-Specific Organic Anion Transporter 1
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism*
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism
  • Pharmacogenetics*
  • Phenotype
  • Polymorphism, Genetic

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Membrane Transport Proteins
  • Organic Anion Transporters
  • SLCO1B1 protein, human