CYP2C9和VKORC1基因检测指导急性肺血栓栓塞症患者个体化华法林抗凝治疗的临床研究

目的评价CYP2C9和VKORC1基因检测指导急性肺血栓栓塞症患者个体化华法林抗凝治疗的临床价值。 方法选择2014年7月至2015年6月天津医科大学总医院的72例急性肺血栓栓塞患者，用PCR及基因芯片技术检测患者CYP2C9和VKORC1基因型。将患者分为基因指导组（34例）和常规对照组（38例）。基因指导组根据国际华法林药物基因组联合会（IWPC）模型和基因型计算华法林预测量，连续给药该剂量3 d，对照组予以3 mg/d华法林持续3 d，于第4天开始两组患者根据INR及临床经验调整华法林药量。所有患者随访12周，在第1，4，6，8，10，12，14，21，28、42、56和84天测INR值，并记录随访期间患者每日服药量。 结果两组患者在VKORCl和CYP2C9基因型分布方面比较，差异没有统计学意义（χ²=0.941，P=0.919）。与对照组相比，基因指导组INR首次达目标范围时间（8.8 ± 3.6）d vs.（10.7 ± 2.9）d；t=2.481，P=0.016]及达稳定剂量时间较短（14.3 ± 6.1）d vs.（19.2 ± 6.5）d；t=3.252，P=0.002]，2周内达稳定剂量比例较高（19/34 vs. 12/38，χ²=4.323，P=0.038）。同时两组患者INR均值随时间变化差异有统计学意义（F=42.016，P<0.001），且在第4、6、8、10、12、14、19、21、28天两组INR值比较差异均有统计学意义（P均<0.05）。 结论CYP2C9和VKORC1基因检测指导急性肺血栓栓塞症患者个体化华法林抗凝治疗能更快达INR目标范围及华法林稳定剂量，在抗凝治疗早期具有指导作用。

Clinical study of warfarin individualized anticoagulation based on CYP2C9 and VKORC1 genotypes for acute pulmonary thromboembolism patients

ObjectiveTo evaluate the clinical application of warfarin individualized anticoagulation based on CYP2C9 and VKORC1 genotypes in patients with acute pulmonary thromboembolism. MethodsSeventy-two patients with acute pulmonary thromboembolism in the General Hospital of Tianjin Medical University from July 2014 to June 2015 were enrolled. The CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR and gene chip technology. The patients were randomly divided into study group (n=34) and control group (n=38). The patients in the study group were given warfarin dose according to the International Warfarin Pharmaeogenetics Consortium (IWPC) at the first 3 days, and the patients in the control group received the dose of 3 mg/d at the first 3 days. Then all the patients adjusted the warfarin dose according to the international normalized ratio (INR) and routine clinical practice. The INR were measured routinely at 1, 4, 6, 8, 14, 21, 28, 42, 56, 84 d, and warfarin dose were recorded everyday. ResultsThe CYP2C9 and VKORC1 genetic polymorphisms in the two groups showed no significant differences (χ²=0.941, P=0.919). Compared with the control group, the first time to INR target range (8.8 ± 3.6) d vs. (10.7 ± 2.9) d; t=2.481, P=0.016] and time-to-stable dose (14.3 ± 6.1) d vs. (19.2 ± 6.5) d; t=3.252, P=0.002] were much shorter, number of stable dosage at 2 weeks (19/34 vs. 12/38, χ²=4.323, P=0.038) were much higher in the study group. Meanwhile, the INR in the two groups were changed over time (F=42.016, P<0.001), and the INR at 4, 6, 8, 10, 12, 14, 19, 21, 28 d in the study group also showed statistical significance (all P<0.05). ConclusionThe warfarin individualized anticoagulation based on CYP2C9 and VKORC1 genotypes can shorten the adjustment time to reach INR target range and warfarin stable dose, and have a guiding role at the early stage of anticoagulation.