Pharmacogenomics of Warfarin

Daly, AK

doi:10.1016/B978-0-12-386882-4.00024-4

Pharmacogenomics of Warfarin

Lookup NU author(s): Professor Ann Daly ORCiD

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Abstract

© 2014 Elsevier Inc. All rights reserved. Warfarin is one of the most widely prescribed drugs worldwide. A variety of factors ranging from patient age to size can affect individual dose requirement but there has been considerable recent interest in genetic factors relevant to dose. There is now a large amount of data showing that genotype for common polymorphisms in the genes encoding the target vitamin K epoxide reductase (VKORC1 G-1639A/C1173T) and the main metabolizing enzyme CYP2C9 (CYP2C9*2 and *3 alleles) are important determinants of individual warfarin dose requirement. Additional less common polymorphisms in these genes together with polymorphisms in other genes relevant to blood coagulation such as CYP4F2 and calumenin may also be predictors of dose, especially in ethnic groups, such as Africans, where there have been fewer genetic studies compared with European populations. Use of relevant genotypes to calculate starting dose may improve safety during the initiation period.Various algorithms for dose calculation, which take patient age, concurrent drugs, and other patient-specific factors together with CYP2C9 and VKORC1 genotype into consideration, have been developed for warfarin and are now being tested in ongoing large randomized clinical trials. One recent study has provided encouraging results suggesting that individualization of warfarin dose on the basis of a dosing algorithm including genotype leads to fewer adverse events and a higher proportion of time within the therapeutic coagulation rate window, but these findings still need confirmation.