Role of warfarin pharmacogenetic testing in clinical practice.
Chronic oral anticoagulation with warfarin is difficult to maintain within the therapeutic range and requires frequent monitoring and dose adjustments. Variations in two genes, VKORC1 and CYP2C9, have been associated with variation in warfarin metabolism among individuals. Patients with CYP2C9*2 and *3 variants have longer times to dose stabilization and are at higher risk of serious and life-threatening bleeding. VKORC1 polymorphisms significantly influence time to first therapeutic warfarin range, and variants in this gene determine low-, intermediate- and high-warfarin dose requirements. The prevalence of CYP2C9 and VKORC1 polymorphisms vary among different ethnic groups, and can account for over 30% of variance in warfarin dose. Recent studies suggest that the pharmacogenomics-guided dosing algorithm can accurately predict warfarin dosage and might reduce adverse events. We aim to review the pharmacogenetics of warfarin metabolism and the clinical role of genetic testing for warfarin therapy.
Tan
Guang-Ming
GM
Prince of Wales Hospital, Hong Kong, China. bryan.yan@cuhk.edu.hk
Wu
Enoch
E
Lam
Yat-Yin
YY
Yan
Bryan P
BP
D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D003362:Cost-Benefit Analysis; D065729:Cytochrome P-450 CYP2C9; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D005006:Ethnicity / Q000235:genetics; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics / Q000191:economics / Q000639:trends; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
D000925:Anticoagulants; 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