The Pharmocogenomics of Warfarin

Mechanism of action of warfarin and roles of CYP2C9 and VKORC1 in modulating anticoagulation. Warfarin exerts its pharmacological effect by inhibiting VKORC1. VKORC1 is the vitamin K cycle enzyme controlling regeneration of reduced vitamin K, an essential cofactor that drives formation of the clotting factors. CYP2C9 is the major P450 enzyme that metabolizes S-warfarin to inactive metabolites. CYP2C9, Cytochrome P4502C9; VKORC1, vitamin K epoxide reductase complex 1, GGCX, gamma-glutamyl carboxylase. Adapted from (31).