摘要目的 对目前已建立的3种华法林个体化给药模型在中国汉族人群中进行验证,评价模型的准确性和临床实用性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对患者进行细胞色素P450 2C9 * 3(CYP2C9*3)、维生素K环氧化物还原酶复合体亚单位1-1639G＞A( VKORC1-1639G＞A)进行基因分型.收集患者的性别、年龄、体质量信息,并记录华法林的实际稳定维持剂量.将相应变量代入Wen、Ohno、IWPC模型,分别计算3种模型的预测剂量.用预测剂量与实际稳定维持剂量的差值(平均绝对差值、百分绝对差值)和相关性回归系数R2比较模型的准确性；用预测剂量落入实际维持剂量±20％范围内(理想剂量)的百分比评价模型的临床实用性.结果 130例心脏机械瓣膜置换术后使用华法林抗凝治疗达稳定维持剂量的患者纳入本研究,用于3个模型的验证.准确性比较:Wen模型的差值最小(3.74 mg/周),其次是Ohno模型(4.07 mg/周),IWPC模型最大(5.05 mg/周)；Wen模型的相关性回归系数R2最大(40.2％),其次是Ohno模型(38.2％),IWPC模型最小(26.7％).临床实用性比较:低剂量组中,Wen模型落入理想剂量范围比例最大(50.0％)；在中剂量组(患者占比最大组)中,3个模型的表现均好,其中Ohno模型落入理想剂量范围比例最大(85.29％)；无患者划入高剂量组.结论 3个模型中,Wen模型最准确；另外,Wen模型在低剂量组患者中临床实用性最好,Ohno模型在中剂量组患者中临床实用性最好.但这些模型均不适用于中国汉族人群.

abstractsObjective To assess whether the existing three types of pharmacogenetics-based Warfarin dosing algorithms appropriately predict the actual maintenance dose in Han Chinese mechanical heart valve replacement patients (n =130 ).Methods The patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR-RFLP.The genotype of CYP2C9,VKORC1 and other information were used to calculate predicted doses.Accuracy of the models was assessed using the absolute value of the difference between predicted dose and actual dose,calculated on both an absolute and percentage basis.Actual weekly dose was also regressed on predicted weekly dose,from which we obtained R2 values.Clinical accuracy of the predictions was assessed by computing the proportion in which the predicted dose was 20％ or more below the actual dose (under dosed),within 20％ of the actual dose (ideally dosed ),or 20％ or greater above the actual dose ( over dosed).Results The average absolute error is the smallest for the predictions made by the Wen model (3.74 mg/wk),followed by the Ohno model(4.07 mg/wk) and IWPC model(5.05 mg/wk).R2 was 40.2％ in the Wen model,38.2％ in the Ohno model and 26.7％ in the IWPC model.When comparing the percentage of patients for whom the predicted doses were ideal,the Wen model works the best (50.0％) in low-dose group (≤21 mg/wk),but the Ohno model works the best (85.29％) in middle-dose group (21 -49 mg/wk),followed by the Wen model.Conclusion The best accuracy is achieved by the Wen model and the best clinical accuracy is obtained by the Ohno model for predicting the actual maintenance dose in Han Chinese mechanical heart valve replacement patients.