The pharmacogenomics of cytochrome P450s: From molecular to clinical application

Abstract

Polymorphisms in genes encoding cytochrome P450s (CYPs) cause interindividual variability in the metabolism of a wide range of structurally diverse substrates including drugs, hormones, lipids, and environmental pollutants. Because P450s account for approximately 75 % of the total drug metabolisms, genetic polymorphisms in P450-encoding genes have garnered a good deal of attention in the context of pharmacogenomics research, resulting in the discovery of a number of clinically relevant P450 genetic polymorphisms. Advances in our understanding of P450 pharmacogenomics enhance the therapeutic efficacy of drugs and reduce their toxicities. In this chapter, we review the pharmacogenomics of major P450s from molecular discovery to clinical application, and discuss the clinical implications of genotype-guided personalized pharmacotherapy.