Influence of CYP2C9 and CYP4F2 gene polymorphisms on stable warfarin dose after cardiac valve replacement / 实用医学杂志

ABSTRACT

Objective To evaluate the influence of cytochrome P450 (CYP2C9 and CYP4F2) polymorphisms on anticoagulant intensity of warfarin after cardiac valve replacement.Methods A total of 136 patients tak ing warfarin after cardiac valve replacement were identified and classified into 4 groupsCYP2C9 wild type group (CYP2C9*1*1),CYP2C9 mutated type group (CYP2C9*3),CYP4F2 rs2108622 wild type group (CC) and CYP4F2 rs2108622 mutated type group (CT or TT).The patients' baseline data,initial dose of warfarin and base INR measurement resuhs were recorded and then the follow-up was conducted.The initial administration of warfarin to INR standard time for the first time,total amount of warfarin and the average daily amount were recorded.Results Patients carrying CYP2C9* 1* 1 had increased time to reach INR target value for the first time (P ＜ 0.05);and the total warfarin doses and average daily dose when INR reached target value were higher than those carrying CYP2C9*3 (P ＜ 0.05).When compared with those in two wild type groups,patients carrying CYP2C9 and CYP4F2 rs2108622 mutated type needed the shortest time when INR reached target value for the first time,and the total warfarin doses and average daily dose when INR first reached target value was the lowest,which showed significant difference (P ＜ 0.05).And when compared with CYP2C9 mutated type group,the INR average time to reach the first target was shortened and the total warfarin dose of patients carrying CYP2C9 and CYP4F2 rs2108622 mutated type was lower (P ＜ 0.05).Conclusion The gene polymorphisms of CYP2C9 and CYP4F2 are significant hereditary factors influencing warfarin dose.Detection of CYP2C9 and CYP4F2 genotypes prior to medication and predicating warfarin dosage may result in lower incidence of over-anticoagulation and reduce the dosage-adjusting time of warfarin.