CYP2C9基因多态性在房颤患者华法林抗凝治疗中的意义

The role of the polymorphism of CYP2C9 in Warfarin anticoagulation therapy for patients with atrial fibrillation

目的研究汉族人群CYP2C9基因多态性对房颤患者华法林抗凝治疗的意义,探讨华法林用药个体差异显著的原因。方法对北京医院住院治疗的符合研究入选标准的100例应用华法林抗凝治疗的房颤患者提取静脉血DNA,并用聚合酶链反应分别从基因组DNA中特异性扩增CYP2C9基因的第3号外显子及第7号外显子,对DNA产物测序分析,计算其基因型和等位基因频率,同时记录患者基本信息、服药期间的华法林用药剂量及凝血功能。结果 100例因房颤应用华法林抗凝治疗患者中共筛选到两种等位基因:CYP2C9*1和CYP2C9*3,等位基因频率分别为96%和4%。同时,CYP2C9基因多态性共检测到两种基因型,以CYP2C9*1/*1基因型常见,基因型频率为92%;其次为CYP2C9*1/*3型,基因型频率为8%。在达到抗凝指标(国际标准化比值INR 2.0~3.0)后,CYP2C9*1/*3突变型患者的华法林维持剂量为(2.14±0.55)mg,低于CYP2C9*1/*1野生型组的平均剂量[(3.17±0.74)mg],两组间剂量差异有统计学意义(P<0.05)。结论 CYP2C9基因多态性与房颤患者华法林抗凝治疗维持剂量有关系,可以部分解释华法林用药个体差异的原因。

Objective To investigate the significance of CYP2C9 gene polymorphism in Warfarin anticoagulation therapy for patients with atrial fibrillation, in order to explore the causes of Warfarin individual difference. Methods The 3rd and 7th exon of CYP2C9 in 100 patients with atrial fibrillation given Warfarin anticoagulation therapy in Beijing Hospital were detected by PCR and restriction enzyme digestion. The genotype and allelic frequencies were calculated and patients information, coagulation function and the individual Warfarin dosage requirements were recorded. Results In this group of patients with atrial fibrillation given Warfarin anticoagulation therapy, two kinds of allele were detected： CYP2C9＊1and CYP2C9＊3, the frequency of ＊1 allele and ＊3 allele was 96% and 4% respectively. CYP2C9＊1/＊1 was the most common genotype, with the frequency of 92%. The frequency of CYP2C9＊1/＊3 was 8% in these 100 patients. After similar target INR range（2.0-3.0） achieved, variant CYP2C9＊1/＊3 homozygotes or heterozygotes required lower daily mean maintain doses [（2.14±0.55） mg] than wild-type CYP2C9＊1/＊1 patients did [（3.17±0.74） mg], with statistically significant difference（P 0.05）. Conclusion Polymorphism of CYP2C9 is associated with Warfarin dose requirements in patients with atrial fibrillation, which is partly the factor causing Warfarin individual difference.