中国药物警戒 ›› 2012, Vol. 9 ›› Issue (4): 202-204.

• 基础及临床研究 • 上一篇    下一篇

CYP2C9和VKORCl基因多态性对肺栓塞患者华法林维持剂量的影响

娄莹1，刘红1，韩璐璐1，谢爽1，高小晶1，段兵1，倪新海2，熊长明2，李一石1，柳志红2，*   

  1. 1 北京协和医学院 中国医学科学院 阜外心血管病医院临床药理中心 卫生部心血管药物临床研究重点实验室，北京 100037；
    2 阜外心血管病医院肺血管病诊治中心，北京100037
  • 收稿日期:2012-02-22 出版日期:2012-04-10 发布日期:2015-08-10
  • 通讯作者: 柳志红,教授,博士生导师,肺血管病的诊治与研究。E-mail：liuzhihong_fw@263.net
  • 作者简介:娄莹，女，博士研究生，主治医师，心血管内科学和心血管药物的临床药理学研究。
  • 基金资助:
    国家科技重大专项（2008ZX09312-018,2011ZX09304,2012ZX09303008-001）

Influence of CYP2C9 and VKORC1 Genetic Polymorphisms on Maintenance Warfarin Dose in Chinese Pulmonary Embolism Patients

LOU Ying1 ,LIU Hong1, HAN Lu-lu1 , XIE Shuang1, GAO Xiao-jing1,DUAN Bing1, NI Xin-hai2 ,XIONG Chang-ming2 , LI Yi-shi1 ,LIU Zhi-hong2*   

  1. 1 Peking Union Medical College and Chinese Academy of Medical Science, Cardiovascular Institute and Fu Wai Hospital, Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, Beijing 100037, China;
    2 Fu Wai Hospital, Pulmonary Vascular Disease Center, Beijing 100037, China
  • Received:2012-02-22 Online:2012-04-10 Published:2015-08-10

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摘要： 目的研究细胞色素P450酶2C9(CYP2C9)及维生素K环氧化物还原酶复合体亚单位1（VKORCl）基因多态性对中国肺栓塞患者华法林维持剂量的影响。方法对108例INR已稳定达标的中国肺栓塞患者，采用TaqMan MGB探针法，检测CYP2C9*2、*3位点和VKORC1-1639A>G位点基因型。记录患者的年龄、性别、体重、身高及华法林日平均剂量。结果VKORC1 -1639AG或GG基因型患者华法林稳定日均剂量明显高于AA基因型患者（5.81±1.93 vs 3.33±1.11mg，P <0.001）;CYP2C9*2或*3变异的患者华法林稳定日均剂量低于无变异的患者（2.57±1.31 vs 3.97±1.67mg，P<0.001）;包括患者性别、年龄、身高、体重、CYP2C9和VKORC1基因型等因素在内的华法林稳定剂量预测模型可解释51.1%左右的华法林稳定剂量个体差异（R2=0.511，P <0.001）。结论CYP2C9和VKORC1基因型检测对指导中国肺栓塞患者个体化应用华法林有一定的临床意义。

关键词: 华法林, 肺栓塞, 稳定剂量, CYP2C9, VKORC1, 基因多态性

Abstract: Objective To evaluate the effect of CYP2C9 and VKORC1 polymorphisms on maintenance warfarin dose in Chinese pulmonary embolism patients. MethodsIn 108 Chinese pulmonary embolism patients whose INR had reached the target value stably, we detected VKORC1 and CYP2C9 gene polymorphisms withTaqMan MGB Probe method, and recorded the mean daily maintenance warfarin dose(mg/d-1), gender, age, weight and height．ResultsThe mean maintenance daily doses of warfarin in patients carrying VKORC1-1639A/G or G/G were much higher than patients carrying VKORC1-1639A/A(5.81±1.93 vs. 3.33±1.11mg, P<0.001);CYP2C9*1/*3 or1/*2 carriers had lower mean maintenance daily doses of warfarin than CYP2C9*1/*1 carriers(2.57±1.31 vs. 3.97±1.67mg, P=0.029）; warfarin maintenance dose algorithm including gender, age, weight, hight, VKORC1 and CYP2C9 gene polymorphisms could explain about 51.1% individual dose requirement(R2=0.511, P<0.001). ConclusionDetection of CYP2C9 and VKORC1 polymorphisms may have clinical significance to guide the individualized warfarin dosage in Chinese pulmonary embolism patients．

Key words: warfarin, pulmonary embolism, maintenance dose, CYP2C9, VKORC1, gene polymorphism