Genetic Determinants of Warfarin Anticoagulation Effect

Warfarin Induction Regimen Based Upon CYP2C9, VKORC1 Factor VII Genotyping, PMR and INR Monitoring, as Compared to the Conventional Regimen: a Prospective Controlled Study

The response to warfarin varies greatly among individuals. Some of this variability can be ascribed to genetic polymorphisms in the gene encoding for CYP2C9, the enzyme mediating the metabolism of S warfarin. In addition genetic polymorphism in other genes (i.e. VKORC1, factor VII) have been shown to account for some of the variability in the response to warfarin irrespective of CYP2C9.The present study has several segments:

1. Evaluation of the relationship between genetic polymorphisms in the genes encoding for CYP2C9, VKORC1 and factor VII and warfarin maintenance dose at steady state. This study is a confirmation of previous data in our own population.
2. Evaluation of relationship between genetic polymorphisms in the genes encoding for CYP2C9, VKORC1 and factor VII and warfarin loading dose during the induction period.
3. Testing the hypothesis that warfarin loading based on the individual's combined CYP2C9, VKORC1 and factor VII genotype may be more efficient and associated with reduced adverse drug effects.

Inclusion Criteria:

• Patients in whom warfarin is about to be initiated
• Desired therapeutic range >2 and <3

Exclusion Criteria:

• Refusal to participate in the study