基因检测预测华法林给药剂量准确性的研究

Coherence between genotype-based prediction dose and actual dose of warfarin

目的:考察华法林IWPC预测剂量与实际剂量的相关性。方法:选取某院2014年11月至2015年8月间住院期间行华法林基因检测的患者97例,记录其基本信息和临床用药情况,利用基因测序的方法检测CYP2C9*2,*3和VKORC1 G>A基因型,并利用IWPC公式预测患者华法林剂量,考察预测剂量与实际剂量相关性。结果:行基因检测的97例患者中,73例服用华法林,42例住院期间INR达标。初始预测剂量中,CYP2C9*3 AA/VKORC1 AA型实际初始剂量在预测剂量范围内的比例为81.13%(43/53例),CYP2C9*3 AC/VKORC1 AA型实际初始剂量在预测剂量范围内的比例为62.50%(5/8例),其余的基因型实际初始剂量在预测剂量范围内的比例较小。维持剂量中,预测周剂量的平均值为19.286 mg,实际维持周剂量平均值为19.958 mg,R=0.415,P=0.562>0.05,预测的维持周剂量与实际维持周剂量无显著差异,且VKORC1 AA/CYP2C9*3 AC和VKORC1 AG/CYP2C9*3 AA2组中预测剂量与实际剂量相关系数分别为0.537和0.916,相关性良好。结论:基因检测预测华法林用药剂量具有一定的准确性,在初始剂量预测中,CYP2C9*3 AA/VKORC1 AA型和CYP2C9*3AC/VKORC1 AA型预测准确性较高;维持剂量预测中,CYP2C9*3 AC/VKORC1 AA和CYP2C9*3 AA/VKORC1 AG预测准确性较高,具有较高临床参考意义。

OBJECTIVE To inspect the coherence between the IWPC predicted dose and the actual dose.METHODS Totally97 warfarin treated patients underwent genotyping test were included in a Hospital between November 2014 and August 2015.Their basic information and clinical medication were recorded,genotypes of CYP2C9＊2,＊3 and VKORC1 G〉A were detected,IWPC formula was used to calculate the warfarin dosage.RESULTS Of 97 patients included,73 patients used warfarin and 42 patients reached the target INR.In initial predicted dose group,the percentage of actual dose in predict dose were81.13%（43/53,CYP2C9＊3 AA/VKORC1 AA）,62.50%（5/8,CYP2C9＊3 AC/VKORC1 AA）,other genotypes were much less.In maintenance dose group,the average dose of predicted weekly dose was 19.286 mg,and the actual weekly dose was 19.958 mg（R=0.415,P=0.562〉0.05）.And the correlation coefficient of predicted dose and actual dose were 0.537 and 0.916 in group VKORC1 AA/CYP2C9＊3 AC and group VKORC1 AG/CYP2C9＊3 AA,and the coherence of these group was good.CONCLUSION Genotypeguided dosing of warfarin is relatively correct.In initial predicted dose group,the CYP2C9＊3 AA/VKORC1 AA and CYP2C9＊3 AC/VKORC1 AA type have high accuracy,while in maintenance predicted dose group,the CYP2C9＊3 AC/VKORC1 AA and CYP2C9＊3 AA/VKORC1 AG have high accuracy,which are important for warfarin anticoagulation therapy.