VKORC1和CYP2C9基因多态性对华法林抗凝初期维持剂量及剂量波动的影响

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摘要目的考察VKORC1和CYP2C9基因多态性对华法林抗凝初期（给药90 d）维持剂量及剂量波动的影响。方法纳入2014年6月～2016年12月在中山大学附属第一医院行人工心脏瓣膜置换术患者201例，经聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法检测VKORC1 rs7294和CYP2C9*3基因型，并分析VKORC1和CYP2C9基因型对华法林持久波动日剂量（LD）和华法林日剂量波动幅度（DD）的影响。结果 VKORC1 rs7294 C＞T和CYP2C9*3的突变频率分别为12.5%、2.5%，均满足哈迪温伯格平衡。CYP2C9*3对LD和DD的影响不明显（P ＞ 0.05）。VKORC1 rs7294 T突变基因携带者的LD和DD均明显高于CC野生纯合子携带者（P ＜ 0.001；P ＜ 0.01）。结论 VKORC1 rs7294 C＞T突变导致患者所需华法林抗凝维持剂量升高，更易发生剂量波动，应该加强国际标准化比值的监测。

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	张舒羽1
	2 许哲3 周守宁2 郑卓玲2 汤世凡2 张希3 黄民2 李嘉丽2

关键词 ：华法林, VKORC1, CYP2C9, 基因多态性, 剂量波动, 心脏机械瓣膜置换术

Abstract：Objective To investigate the effect of VKORC1 and CYP2C9 gene polymorphism on the lasting dose and dose fluctuation of warfarin at the initial anticoagulation phase (90 d after administration). Methods A total of 201 patients who underwent mechanical heart valve replacement in the First Affiliated Hospital, Sun Yat-sen University from June 2014 to December 2016 were recruited. The genotypes of VKORC1 rs7294 and CYP2C9*3 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The effects of VKORC1 and CYP2C9 genotypes on daily warfarin lasting dose (LD) and daily warfarin dose difference (DD) were analyzed. Results The mutation frequency of VKORC1 rs7294 C＞T and CYP2C9*3 was 12.5% and 2.5%, respectively, meeting the hardy weinberg equilibrium. There was no significant effect of CYP2C9*3 on LD and DD （P ＞ 0.05）. LD and DD of VKORC1 rs7294 T mutant carriers were significantly higher than that of CC wild homozygous carriers (P ＜ 0.001,P ＜ 0.01). Conclusion The mutation of VKORC1 rs7294 C＞T leads to the increase of warfarin anticoagulant lasting dose required by patients, which is more likely to cause dose fluctuation. Therefore, the monitoring of international standardized ratio should be strengthened.

Key words： Warfarin VKORC1 CYP2C9 Gene polymorphism Dose volatility Mechanical heart valve replacement

基金资助:国家重点研发计划精准医学研究重点专项项目（2017YFC0909300）；
国家卫生健康委医药卫生科技发展研究中心重大新药创制科技重大专项项目（2018ZX09721003-005-001）。

通讯作者: 李嘉丽（1982-），女，博士，副教授，硕士生导师；研究方向：临床药理学、药物代谢与药物基因组学。

作者简介: 张舒羽（1990-），女，博士；研究方向：药物代谢与药物基因组学。

引用本文:

张舒羽1,2 许哲3 周守宁2 郑卓玲2 汤世凡2 张希3 黄民2 李嘉丽2. VKORC1和CYP2C9基因多态性对华法林抗凝初期维持剂量及剂量波动的影响[J]. 中国医药导报, 2019, 16(31): 34-36,45.
ZHANG Shuyu1,2 XU Zhe3 ZHOU Shouning2 ZHENG Zhuoling2 TANG Shifan2 ZHANG Xi3 HUANG Min2 LI Jiali2. Effect of VKORC1 and CYP2C9 gene polymorphism on the lasting dose and dose fluctuation at the initial anticoagulation phase. 中国医药导报, 2019, 16(31): 34-36,45.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2019/V16/I31/34

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