药物基因组学方程对上海患者华法林抗凝治疗稳定剂量预测准确性的评估

Evaluation on the stable dose prediction accuracy of Warfarin anticoagulant therapy by pharmacogenetics among Shanghai patients

目的在接受华法林抗凝治疗肺栓塞和心颤患者的上海患者人群中,验证华法林药物基因组学稳定剂量预测方程的准确性。方法收集已达华法林稳定剂量的198例患者完整的临床资料,采集每位患者枸橼酸钠抗凝1∶9抗凝的外周血1.8 m L,抽提全血基因组DNA后采用高分辨率溶解曲线法检测其VKORC1-1173C>T和CYP2C9*2、CYP2C9*3基因型。采用较多使用的符合筛选条件的4个华法林稳定剂量预测模型[包括IWPC模型(基于混合种群构建)、WEN模型(基于中国台湾人群构建)、HUANG模型(基于中国大陆人群构建)及OHNO模型(基于日本人群构建)]。采用绝对误差均值(MAE)和预测百分比2个指标评价并比较各模型预测准确性。结果在4个预测模型中,HUANG、OHNO及WEN 3个预测模型及固定剂量方案计算的MAE<±1.0mg/d,理想预测百分比>40%,其中MAE最低的模型为HUANG模型。理想预测百分比最高的模型为OHNO。结论采用亚洲人群建立的基因导向结合基本临床资料的华法林稳定剂量预测模型可以较好预测服用华法林的部分上海患者的药物剂量,具有一定临床应用价值。

Objective To validate the stable dose prediction accuracy of Warfarin anticoagulant therapy by pharmacogenetics among Shanghai patients with pulmonary embolism and heart fibrillation. Methods The complete clinical data of 198 patients with stable Warfarin dose were collected. The VKORC1-1173 C T,CYP2C9 ＊ 2 and CYP2C9＊ 3 genotypes were detected by polymerase chain reaction-high resolution melting technique after whole blood genomic DNA extraction with peripheral blood 1. 8 m L of sodium citrate anticoagulation 1 ∶ 9. The 4 prediction algorithms,including IWPC for mixed population,WEN for Chinese Taiwan population,HUANG for Chinese mainland population and OHNO for Japanese,were evaluated and compared by mean absolute error（ MAE） and prediction accuracy. Results The MAE of HUANG,OHNO and WEN in 4 prediction algorithms and fixed dose model was ± 1. 0 mg / d with ideal prediction percentage 〉40%,with the minimum MAE in HUANG. The ideal prediction algorithm with highest percentage was OHNO. Conclusions The Warfarin stable dose algorithms by pharmacogenetics for Asian population combined with basic clinical information can predict the dose of Warfarin among Shanghai with clinical application significance.