Pharmacogenetics of warfarin

  1. Lookup NU author(s)
  2. Professor Farhad Kamali
  3. Dr Hilary Wynne
Author(s)Kamali F, Wynne H
Publication type Article
JournalAnnual Review of Medicine
Year2010
Volume61
Issue1
Pages63-75
ISSN (print)0066-4219
ISSN (electronic)1545-326X
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Warfarin is a drug with a narrow therapeutic index and a wide interindividual variability in dose requirement. Because it is difficult to predict an accurate dose for an individual, patients starting the drug are at risk of thromboembolism or bleeding associated with underdosing or overdosing, respectively. Single nucleotide polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR) genes have been shown to have a significant effect on warfarin dose requirement. Other genes mediating the action of warfarin make either little or no contribution to dose requirement. Although the polymorphisms in CYP2C9 and VKORC1 explain a significant proportion of the interindividual variability in warfarin dose requirement, currently available evidence based on a few small studies relating to the use of pharmacogenetics-guided dosing in the initiation of warfarin therapy has not shown improved outcomes in either safety or efficacy of therapy. Better clinical evidence of beneficial effects on patient outcome, particularly at the extremes of the dose requirements in geographically and ethnically diverse patient populations, is needed before the role of a pharmacogenomic approach to oral anticoagulation therapy in clinical practice can be established.
PublisherAnnual Reviews
URLhttp://dx.doi.org/10.1146/annurev.med.070808.170037
DOI10.1146/annurev.med.070808.170037
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