【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 rs7294C>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。更多还原

【Abstract】 Objective To investigate the effect of VKORC1 and CYP2 C9 gene polymorphism on the lasting dose and dose fluctuation of warfarin at the initial anticoagulation phase(90 d after tients 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 CYP2 C9*3 were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The effects of VKORC1 and CYP2 C9 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 CYP2 C9*3 was 12.5% and 2.5%, respectively, meeting the hardy weinberg equilibrium. There was no significant effect of CYP2 C9*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.更多还原