Vol 68, Supp. V (2010)
Reviews
Published online: 2010-11-25
Optimalisation of treatment with vitamin K antagonists - the role of gene polymorphisms
DOI: 10.33963/v.kp.79582
Abstract
The magnitude of a maintenance vitamin K antagonist (VKA) dose during anticoagulant therapy depends not only on clinical,
environmental, and demographic factors, but also on genetic factors. Known genetic polymorphisms explain 40-50% of the
variance in VKA dosing. Polymorphisms of two genes encoding enzymes involved in vitamin K and/or VKA metabolism such
as vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 isoform (CYP2C9) play a key role in
this variance. Polymorphisms of cytochrome P450 4F2 isoform (CYP4F2), apolipoprotein E (APOE) and gamma-glutamyl
carboxylase (GGCX) are of minor or negligible importance. In European populations, 3 haplotypes of VKORC1, VKORC1*2,
VKORC1*3 and VKORC1*4 - have been identified and they determined 99% of genetic variability of this enzyme. The
presence of -1639G>A VKORC1 polymorphism is associated with increased VKA dose requirements. Allelic variants of CYP2C9*2
and CYP2C9*3 (found in 8-12% and 3-8% of individuals, respectively) increase the risk of haemorrhage due to slow VKA
metabolism, especially at the therapy initiation. Pharmacogenetic algorithms incorporating VKORC1 and CYP2C9 genotypes help
to predict the VKA dosage, particularly if the dose requirements are low or moderate. However, there is no compelling evidence
showing reduced risk for clinical adverse events during VKA therapy following the identification of the patient’s genetic profile.
Kardiol Pol 2010; 68, supl. V: 428-435
Kardiol Pol 2010; 68, supl. V: 428-435
Keywords: vitamin K antagonistsgenetic polymorphismvitamin K epoxide reductasecytochrome P450resistancepharmacogeneticsstable anticoagulation