Understanding the pharmacogenetic approach to warfarin dosing.
Warfarin remains the drug of choice for long-term anticoagulation management in a variety of conditions. Despite an established role in prevention of thromboembolic events such as stroke, warfarin continues to be underutilized because of its association with serious drug-related adverse events. Lacking alternative therapeutic approaches, intensive research in the past decade has focused on making anticoagulation with warfarin safer. Much emphasis has been placed on defining factors associated with the wide individual variability in warfarin dose. Polymorphic sites in three genes, cytochrome P450 (CYP) 2C9, vitamin K 2,3 epoxide reductase complex 1 (VKORC1), and CYP4F2, have been shown to affect stable warfarin dose. An overview of the persistent issues related to warfarin therapy and our current understanding of the genetic and clinical factors affecting warfarin dosing is presented. Finally, unresolved issues in improving clinical care of warfarin patients and future directions are provided.
Glurich
Ingrid
I
Office of Scientific Writing and Publications, Marshfield Clinic Research Foundation, Marshfield, WI, USA. glurich.ingrid@mcrf.mfldclin.edu
Burmester
James K
JK
Caldwell
Michael D
MD
D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D064420:Drug-Related Side Effects and Adverse Reactions; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics; D020521:Stroke / Q000517:prevention & control; D013923:Thromboembolism / Q000517:prevention & control; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D000925:Anticoagulants; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases