Pharmacogenetics of oral anticoagulants

Understanding the basis for the observed wide interindividual variation in the dose requirement for the oral anticoagulants should facilitate the safer use of these widely prescribed drugs. Factors that include patient age, body weight and concomitant medications are well known to affect dose requirement and in a large number of recent pharmacogenetic studies, it has been demonstrated that the common variant CYP2C9 alleles are also good predictors of dose requirement, although they fail to account for all the observed interindividual variability. Since pharmacokinetic factors seem to be major contributors to the variability, the possibility that additional CYP2C9 polymorphisms or other polymorphisms affecting anticoagulant disposition could also predict dose is discussed. In addition, the relevance with regard to dose requirement of polymorphism in the recently discovered vitamin K epoxide reductase gene, which encodes the target gene for oral anticoagulants, is considered.