The Significance Of The Mutation Of Cytochrome P4502C9 In Anticoagulation Therapy With Warfarin

Background:Patients underwent prosthetic valve implantation should take anticoagulation therapy. Single using of dicumarol is widely accepted. Warfarin, a synthesized version of dicumarol,is 5 to 10 times stronger than the original compound and is the most commonly used oral anticoagulant.Clinical using tablet of warfarin is composed of S-warfarin and R-warfarin and the former is the main component. Individual difference exists in patients receiving warfarin ,hence, it's not easy to predict warfarin maintenance dose of a single patient.The mutation of CYP2C9 is an important cause.Aflexible dose induction protocol for hospital in-patients with monitoring of INR over the first 4 days of treatment uses the protocol dose on day 4 to predict maintenance dose with a 69%success rate. The metabolism of warfarin have been studied widely and deeply abroad.There are some researches in CYP2C9 that involved in the metabolism of warfarin.The determination of CYP2C9 has been done in those patients with high sensitivity to warfarin.However,there is quite few report about the association between clinical significance and the CYP2C9.In the People's Republic of China, CYP2C9 has not been studied yet,and the distribution of CYP2C9 among people all over china is not clear.The clinical significance of the CYP2C9 mutation is completely unkown.Objective:To observe the association of Genetic polymorphism of cytochrome CYP2C9 with warfarin maintenance dose requirement and improve the accuracy and safety of warfarin administration.Methods:44 patients underwent heart valve prosthesis implantation were divided into two group, G≤1.5mg/m2 as G1 group,G>1.5mg/m2 as G2 group(G= warfarin maintenance dose requirement/body surface area). Polymorphism of cytochrome CYP2C9 were determined by PCR .Results:The mutation rate of CYP2C9Ile359 is higher in those people with lower warfarin maintenance dose requirement.There are no CYP2C9Arg 144 , Tyr35 8 and Gly417 variant detected. Conclusion:(S)-warfarin metabolism decreases in patients with P4502C9 Ile359 allelic variant.