Warfarin Genotyping

Warfarin has a narrow therapeutic window; under medicating increases the risk for thrombosis and overmedicating increases the risk for cerebrovascular accidents. Warfarin therapy has one of the highest rates of severe adverse drug reactions. The cytochrome P450 2C9 gene (CYP2C9) encodes an enzyme that metabolizes the more active isomer of warfarin (S-Warfarin) to inactive products. Polymorphisms in this gene decrease the activity of the enzyme and may cause increases in serum warfarin and overmedicating, driving INR above the therapeutic target level. The second gene (VKORC1) encodes vitamin K epoxide reductase complex subunit-1 (VKORC1), the target of warfarin therapy.

A polymorphism within the promoter of VKORC1 decreases expression of the gene, decreasing the availability of vitamin K. This may cause increases in serum warfarin and overmedicating, driving INR above the therapeutic target level.Therefore, understanding genotype of these two genes helps in deciding the warfarin dosage for a patient.