The pharmocogenomics of warfarin: closing in on personalized medicine.
Warfarin, a coumarin anticoagulant, is used worldwide for the treatment and prevention of thromboembolic disease. Warfarin therapy, however, can be difficult to manage because of the drug's narrow therapeutic index and the wide interindividual variability in patient response. It is now clear that genetic polymorphisms in genes influencing metabolism (CYP2C9) and pharmacodynamic response (VKORC1) are strongly associated with warfarin responsiveness. Optimal warfarin dosing in turn drives other positive anticoagulation-related outcomes. Therefore, a strong basic science argument is emerging for prospective genotyping of warfarin patients. Effective clinical translation would establish warfarin pharmacogenomics as a heuristic model for personalized medicine.
Rettie
Allan E
AE
Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA. rettie@u.washington.edu
Tai
Guoying
G
D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000502:physiology; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D013923:Thromboembolism / Q000188:drug therapy*; D014812:Vitamin K / Q000378:metabolism; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000378:metabolism / Q000494:pharmacology*
D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases