CYP2C9遗传多态性与华法林剂量和抗凝效果的关系研究

郑策;梅丹;管珩

中国药学杂志 ›› 2008, Vol. 43 ›› Issue (11) : 862-865.

中国药学杂志 ›› 2008, Vol. 43 ›› Issue (11) : 862-865.
论著

CYP2C9遗传多态性与华法林剂量和抗凝效果的关系研究

  • 郑策;梅丹;管珩
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Effect of CYP2C9 Genetic Polymorphisms on Warfarin Dosage and Anticoagulation

  • ZHENG Ce,MEI Dan*,GUAN Heng
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摘要

目的初步探讨入选的中国汉族服华法林患者CYP2C9*2和CYP2C9*3遗传多态性对华法林剂量和抗凝效果的影响。方法收集123名服用华法林的汉族患者血标本,记录服药期间的剂量、INR值及出血情况,PCR-RFLP法检测CYP2C9基因型,将患者按CYP2C9*1纯合体和CYP2C9*3杂合体分为2组,探讨CYP2C9遗传多态性对华法林剂量和抗凝效果的影响。结果CYP2C9*1纯合体组和CYP2C9*3杂合体组华法林稳态剂量(P<0.01)、治疗初始阶段抗凝过量的发生率(P<0.01)、达稳定剂量-效应关系的时间(P<0.01)均有显著差别。CYP2C9*1纯合体组和CYP2C9*3杂合体组华法林治疗初始阶段出血的发生率无显著差异(P>0.05)。结论与CYP2C9*1纯合体组比较,CYP2C9*3杂合体者华法林的日维持剂量明显降低,抗凝过量的发生率明显增加,达稳定剂量-效应关系的时间显著延长,但治疗初始阶段出血的风险并没有增加。CYP2C9突变的筛选可以帮助临床调整华法林剂量,减少不良反应的发生。

Abstract

OBJECTIVE To assess the influence of CYP2C9 genetic polymorphisms on warfarin dosage and anticoagulation effect in Chinese warfarin-treated patients of Han nationality.METHODS Blood samples for genotyping were collected from 123 warfarin-treated patients,and the warfarin dosage,INR value and bleeding events were recorded.Patients were divided into 2 groups according to CYP2C9 genotype.The data were analyzed by statistical analysis to evaluate the influence of CYP2C9 genetic polymorphisms on warfarin dosage and anticoagulation effect.RESULTS There were significant differences between CYP2C91 homozygotes and CYP2C93 heterozygotes in warfarin maintenance dosage(P<0.01),the frequencies of overanticoagulation in warfarin initiation therapy(P<0.01) and the duration of achieving stable dose-effect relation(P<0.01).However,there was no difference in the frequencies of bleeding events between CYP2C91 homozygotes and CYP2C93 heterozygotes.CONCLUSION Compared with CYP2C91 homozygotes,CYP2C93 heterozygotes were associated with a decreased warfarin maintenance dosage,an increased risk of overanticoagulation and longer time to achieve stable dosage-effect relation,but were not associated with an increased risk of bleeding events.Screening for CYP2C9 variants may allow clinicians to develop warfarin dosing protocols for reducing the risk of adverse drug reactions in patients treated with warfarin.

关键词

CYP2C9 / 遗传多态性 / 华法林

Key words

CYP2C9 / polymorphism / warfarin / dosage

引用本文

导出引用
郑策;梅丹;管珩. CYP2C9遗传多态性与华法林剂量和抗凝效果的关系研究[J]. 中国药学杂志, 2008, 43(11): 862-865
ZHENG Ce;MEI Dn;GUN Heng. Effect of CYP2C9 Genetic Polymorphisms on Warfarin Dosage and Anticoagulation [J]. Chinese Pharmaceutical Journal, 2008, 43(11): 862-865

参考文献

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