Pharmacogenetics of Cytochrome P450 2D6: A Translational Medicine Perspective

With rapid scientific advances in the postgenomic era, pharmacogenomics has developed into an important area of translational medicine research. Pharmacogenetics studies the variability in drug response between different patient genotypes. By using patient genomic information, this bench-to-bedside research approach aims to develop more effective targeting of drug therapy in clinical practice. This will potentially reduce the risk of adverse drug reactions and avoid treatment failure. One of the important areas of pharmacogenetic variability is in drug metabolism via the cytochrome P450 (CYP) enzyme system. Cytochrome P450 2D6 (CYP2D6) metabolises up to 30% of commonly used drugs but this enzyme displays extensive genetic polymorphism. The approval of CYP2D6 genotype testing by the FDA in 2005 has put this enzyme at the cutting-edge of research into personalised medicine. The effects of CYP2D6 genetic polymorphism on tamoxifen metabolism and clinical outcomes in breast cancer patients is currently an important area of translational research. This review article covers recent progress in CYP2D6 pharmacogenomics and its applications to translational medicine.