单核苷酸多态性与华法林初始抗凝疗效和维持剂量的研究  

Research on single nucleotide polymorphism with initial anticoagulative effect and maintenance dose of Warfarin

作　　者：吴炯[1] 李军[2] 邬升超 张春燕 宋斌斌[1] 王蓓丽[1] 郭玮[1] 潘柏申[1] 

机构地区：[1]上海复旦大学医学院附属中山医院检验科,上海200032 [2]上海复旦大学医学院附属中山医院心外科,上海200032

出　　处：《检验医学》2015年第7期707-714,共8页Laboratory Medicine

基　　金："十二五"国家科技支撑计划资助项目(2012BAI37B01);国家临床重点检验专科建设项目

摘　　要：目的筛选华法林初始抗凝治疗疗效和华法林维持剂量存在显著影响的基因因素。方法初始抗凝疗效组:选取进行心脏瓣膜置换的汉族患者212例,以术后4 d为观测期限,根据设立初始抗凝疗效的观测指标△INR4-1[即观测期结束时的国际标准化比值(INR)与初始INR的差值],筛选出对于该指标存在显著影响的基因因素。同时观查上述因素与其它终点事件如INR>3、INR>4和3 d内是否入窗等是否相关。维持剂量组:选取服用华法林3个月以上的门诊患者266例,需满足相隔7 d以上、在服用相同剂量华法林的情况下,2次INR检测结果均在治疗窗内。筛选显著影响的基因因素。结果在初始抗凝疗效组中,CYP2C9(rs1057910)、VKORC1(rs9923231)和VKORC1(rs2292566)对△INR4-1有明显影响;CYP2C9(rs1057910)和EPHX1(rs2292566)对3 d内INR是否进入治疗范围有明显影响(P<0.001、P<0.05)。在维持剂量组中,CYP2C9(rs1057910)和VKORC1(rs9923231)对每日及每周华法林剂量均有明显影响(P<0.001)。结论 CYP2C9(rs1057910)、VKORC1(rs9923231)和EPHX1(rs2292566)对于华法林初始抗凝疗效有明显影响。CYP2C9(rs1057910)、VKORC1(rs9923231)对华法林维持剂量有明显影响。Objective To screen genetic factors influencing Warfarin initial anticoagulative effect and maintenance dose. Methods A total of 212 Chinese Han mechanical heart valve replacement patients were enrolled as initial anticoagulative effect group. △INR4-1[the difference between international normalized ratio（ INR） at the end of observation and initial INR] was used as an index to screen genetic factors during 4 d after their operations. The obtained results were needed to be identified whether they were associated with other endpoint events like overanticoagulation（ INR〉 3 and INR 〉4） and time to first therapeutic INR in 3 d. In the maintenance dose group,266 Chinese Han outpatients who had been taking Warfarin for over 3 months were enrolled. Warfarin maintenance dose was defined as the dose that led to the patients＇ INR within the therapeutic range measured at least 7 d,which was used to screen genetic factors. Results In the initial anticoagulative effect group,CYP2C9（ rs1057910）,VKORC1（ rs9923231） and VKORC1（ rs2292566） were associated with △INR4-1（ P〈0. 05）,and CYP2C9（ rs1057910） and EPHX1（ rs2292566） were associated with time to first therapeutic INR（ P〈0. 001,P〈0. 05）. In the maintenance dose group,CYP2C9（ rs1057910） and VKORC1（ rs9923231） were associated with daily and weekly maintenance doses（ P〈0. 05）. Conclusions CYP2C9（ rs1057910）,VKORC1（ rs9923231） and EPHX1（ rs2292566） show strongly association with Warfarin initial anticoagulative effect. CYP2C9（ rs1057910） and VKORC1（ rs9923231） are significant factors for maintenance dose.

关 键 词：华法林 单核苷酸多态性 初始抗凝疗效 维持剂量 

分 类 号：Q503[生物学—生物化学]