应用vkorc和cyp2c9基因多态性准确评估患者使用华法林的剂量.pdf

中文摘要 应用VKORC1 和CYP2C9 基因多态性准确评估患者使用华法林的剂量 明显低于其他基因型，并且根据遗传药理学公式计算的华法林剂量与临床治疗剂量 之间无显著性差异(P=0.07) 。 结论：应用基因测序方法检测VKORC1 及CYP2C9 基因多态性为根据药理学公 式准确预测华法林的治疗剂量奠定了基础。 关键词：华法林；VKORC1 ；CYP2C9 ；药理学公式 作 者：Agustinus Wijaya 指导教师：蒋廷波 II The Accuracy of Warfarin Dosage Based on VKORC1 and CYP2C9 Abstract The Accuracy of Warfarin Dosage Based on VKORC1 and CYP2C9 Abstract Background: Warfarin, a Coumadin derivative, is the most prescribed anticoagulant worldwide which has a narrow therapeutic window. Warfarin is metabolized by the hepatic cytochrome P450 enzyme expressed by the CYP2C9 gene. Warfarin’s anticoagulant effect is mediated by the enzyme VKORC1, which is the target enzyme inhibited by warfarin. Variation in the CYP2C9 gene causes some patients to have slow metabolism of warfarin and a longer half-life the drug, resulting in higher than usual blood concentrations of warfarin and greater anticoagulant effect. Objective：The aim of this study is to assess the accuracy of warfarin dosage based on VKORC1 and CYP2C9. Methods: Blood samples were taken from 44 patients. We compared the warfarin dosage between on genotype (according to ) and treatment dosage with INR value within 2.0-3.0. Results: The majority Chinese people on our study had VKORC1 homozygous AA (90.9%), rarely had VKORC1 heterozygous AG (9.1%), and we cannot find a patient with homozygous GG. For CYP2C9 genotype, mostly patients had wildtype variant (CYP2C9*2 CC and CYP2C9*3 AA). The warfarin dosage for patients with VKORC1 AA and CYP2C9*3 AC is lower than the others genotype vari