Human CYP2C9 and VKORC1 Gene Polymorphism

Warfarin is an oral anticoagulant commonly used in clinical practice currently, which is mainly intended for the prevention and treatment of thromboembolic diseases. However, warfarin has a limited treatment window and varies greatly among different races and individuals. Statistics have indicated that the difference of stable dose in different individuals can be more than 20 times. The adverse reaction bleeding occurs in 15.2% of the patients taking warfarin each year, of which 3.5% develop fatal bleeding. Pharmacogenomic studies have shown that genetic polymorphism of target enzyme VKORC1 and metabolic enzyme CYP2C9 of warfarin is an important factor affecting the difference in the dose of warfarin. Warfarin is a specific inhibitor of vitamin K epoxide reductase (VKORC1), and thus inhibits clotting factor synthesis involving vitamin K and provides anticoagulation. A large number of studies have indicated that the gene polymorphism of VKORC1 promoter is the most important factor affecting the race and individual differences in the required dose of warfarin. Warfarin is metabolized by CYP2C9, and its mutants greatly slower metabolism of warfarin. Individuals using warfarin have a higher risk (twice to three times higher) of bleeding in the early stage of use.