基于CYP2C9和VKORC1基因多态性预测老年房颤患者使用华法林的稳定剂量

目的:探讨CYP2C9和VKORC1基因多态性对房颤患者华法林稳定剂量的影响,建立适合汉族人群老年房颤患者的华法林给药模型,指导华法林个体化抗凝治疗。方法:对200例口服华法林抗凝的老年患者进行CYP2C9和VKORC1基因分型,比较不同基因型房颤患者华法林日均稳定剂量的差异。采用多元线性回归分析法依据CYP2C9和VKORC1基因型、年龄、身高、体质量、合并用药建立华法林稳定剂量计算公式。结果:INR稳定在2.0～3.0之间时,CYP2C9*1/*1基因型患者日均使用华法林剂量(3.87±0.71)mg显著高于CYP2C9*3基因型患者(1.05±0.59)mg;VKORC1-1639AA基因型患者日均使用华法林剂量(2.94±1.03)mg显著低于VKORC1-1639GA/GG基因型患者(5.76±1.12)mg。通过多元线性回归分析得出华法林稳定剂量公式,建立的回归模型中包含年龄、体质量、合并用药、CYP2C9*3和VKORC1-1639基因型,该模型能解释约56.5%个体间华法林剂量差异。结论:基于CYP2C9和VKORC1基因多态性建立的华法林稳定剂量预测公式,能帮助指导华法林在老年房颤患者中的抗凝治疗。

Predicting stable dose of warfarin in elderly patients with atrial fibrillation based on CYP2C9 and VKORC1 polymorphisms

OBJECTIVE To investigate the effect of CYP2C9 and VKORC1 polymorphisms on the stable dose of warfarin in patients with atrial fibrillation, and to establish a warfarin administration model suitable for elderly patients in Han population to guide warfarin individualized anticoagulant therapy.METHODS 200 warfarin-treated elderly patients with atrial fibrillation were genotyped according to CYP2C9 and VKORC1, and then compared the daily stable doses of warfarin in these patients with different genotypes. A multiple linear regression analysis was used to establish a warfarin stabilizing dose formula based on CYP2C9 and VKORC1 genotypes, age, height, weight, and drug combination.RESULTS When INR was stable between 2.0 and 3.0, the average daily warfarin dose in patients with CYP2C9*1/*1 genotype (3.87±0.71) mg was significantly higher than that in patients with CYP2C9*3 genotype(1.05±0.59) mg; the average daily warfarin dose in patients with VKORCl-1639AA genotype (2.94±1.03) mg was significantly lower than that in patients with VKORCl-1639GA/GG genotype(5.76±1.12) mg. Warfarin stabilizing dose formula was obtained by multiple linear regression analysis. The established regression model include age, weight, drug combination, CYP2C9*3 and VKORCl-1639 genotypes. This model could explain about 56.5% individual warfarin dose difference.CONCLUSION The warfarin stabilizing dose formula established based on CYP2C9 and VKORC1 polymorphisms can help guide the use of warfarin in elderly patients with atrial fibrillation.