华法林基于药物基因组学个体化给药方案的评价  

Evaluation of warfarin individualized medication based on pharmacogenomics

作　　者：刘俊[1] 徐航[2] 葛卫红[2] 陈小芳[2] 

机构地区：[1]皖南医学院弋矶山医院药剂科,安徽芜湖241001 [2]南京大学医学院附属南京鼓楼医院,江苏南京210008

出　　处：《中国医院药学杂志》2013年第22期1857-1862,共6页Chinese Journal of Hospital Pharmacy

摘　　要：目的:评价CYP2C9和VKORC1基因检测在指导华法林抗凝治疗中的作用。方法:按照设定的标准选取南京鼓楼医院2012年1月-2012年6月行心脏瓣膜手术患者407例,将其分为试验组和对照组,所有患者术后给予华法林抗凝治疗。试验组患者采用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)和测序技术对CYP2C9和VKORC1基因进行检测,根据患者基因型和国际华法林药物基因组联合会(IWPC)模型确定患者华法林首次剂量和预测剂量,并根据国际标准化比值(INR)监测结果调整华法林至合适剂量,对照组直接根据INR监测结果调整华法林至合适剂量。比较华法林实际稳定剂量与预测剂量之间的差异以及试验组和对照组在华法林抗凝治疗时间、华法林稳定剂量、INR达标率等方面的差异。结果:试验组患者CYP2C9*3基因以AA型为主(95.07%),AC为4.93%,VKORC1-1639基因AA型81.77%,GA型17.24%,GG型0.99%;试验组和对照组华法林用药时间、华法林稳定剂量以及两组患者住院期间不良反应的发生率无统计学差异(P>0.05),但试验组华法林在用药3 d,5 d及出院前抗凝强度达标率均明显高于对照组(P<0.01);试验组华法林预测剂量(3.36±0.77)mg·d-1,明显高于华法林稳定剂量(3.00±1.23)mg·d-1(P=0.000),且华法林预测剂量与稳定剂量之间存在相关性(P=0.000,r=0.332,R2=0.110)。结论:CYP2C9和VKORC1基因检测在指导华法林抗凝治疗中具有一定参考价值,但亦存在局限性,有待于进一步临床验证。OBjJCTIVE To assess the role of the genotype of CYP2C9 and VKORC1 detection in anticoagulant therapy with warfarin. METHODS Based on the specified standard,407 patients with cardiac valve surgery in Nanjing Drum Tower Hospital who were divided into the test group and the control group from January 2012 to June 2012 were enrolled in the study,and they were received warfarin and regulated the doses of warfarin to the proper maintain doses by the results of international normal ized ratio（INR）. As well, all the patients＇ CYP2C9 and VKORC1 genetic polymorphisms in the test group were detected by PCR-RELP and sequencing technology. The genotype of CYP2C9 and VKORC1 and other information were used to calculate predicted doses and compared the difference between actual doses and predicted doses as well as warfarin anticoagulant therapy time,warfarin stable dose and INR target rate in the two groups. RESULTS In the test group, AA and AC were 95.07 ~ and 4. 93% separately in CYP2C9 ＊ 3, and VKORC1-1639AA 81.77%, GA 17. 24% and GG 0. 99%. There were no significant difference in warfarin use time, warfarin stable dose and the occurrence of adverse reactions in the two groups （P〉0. 05）, but in the test group, anticoagulation intensity target rate of warfarin in the first three days, fifth day and before discharge were signifi cantly higher than those in the control group （P〈0. 01 ）. warfarin prediction dose （3.36 ± 0. 77） mg.d ＊ was much higher than warfarin stable dose （3.00 ± 1.23）mg·d^-1 （P = 0. 000） and there was correlation between warfarin prediction dose with stability dose （P=0. 001）,r= 0. 332,R2 = （t. 110）. CONCLUSION There is certain reference value for CYP2C9 and VKORC1 gene detection in guiding warfarin anticoagulant therapy,hut there also exists limitation, which needs to be further clinical verification.

关 键 词：华法林 基因多态性 细胞色素P4502C9 维生素K环氧化物还原酶复合体亚单位1 个体化给药 

分 类 号：R952[医药卫生—药学]