Warfarin is an anticoagulant, which works as a VKORC1 antagonist and is the substrate of the CYP2C9 enzyme. The genetic variations in the CYP2C9*2 and VKORC1 affect the metabolism and the effect on warfarin. The enzyme CYP2C9 is a phase I enzyme that metabolizes drugs like S-warfarin, NSAIDs, and Phenytoin. The enzyme CYP2C9 has over 50 alleles defined which contributes to its polymeric nature. Changes in any of these alleles significantly affect the action of the enzyme and thus, the metabolism of the drugs like S-warfarin. The changes in the metabolic activity of CYP2C9 can be attributed to two genetic changes: CYP2C9*2 and CYP2C9*3. A change in the CYP2C9*2 encodes a change in the amino acid located on the outer side of the enzyme. And the…show more content… A mutation in both of these genes is worse than in just one of them. This is because now there is a combined effect of both of these mutations. A standard dose of warfarin will show its effect by blocking the effect of VKORC1, which would result in blocking of coagulating factors and reduced coagulation. However, the patients who have both of these genetic variations will undergo an enhanced effect anticoagulating effect of warfarin. This can be explained as the standard dose of warfarin will target the little amount of coagulating factors produced by the VKORC1 and there will be no coagulating effect in the body (liver). A standard dose of warfarin will not be metabolized in the body at the expected rate due to the reduced metabolizing capability of the CYP2C9 enzyme. This would then slow down the clearance of warfarin and prolong the effect of S-warfarin in the body. Consequently, a standard dose will cause more anticoagulation and the increase the risk of bleeding in the body. It is very important for healthcare providers to take these mutations into account to predict a gene based therapy, optimize the warfarin therapy, and minimize the adverse drug
