基于房颤患者CYP2C9和VKORC1基因型、年龄、身高建立并评价华法林给药剂量计算公式  

Warfarin-dosing algorithm based on CYP2C9 and VKORC1 genotypes,age and height of patients with atrial fibrillation

作　　者：蒋年新[1] 葛俊炜 鲜玉琼[1] 黄少鹰[1] 李岩松[1] 

机构地区：[1]上海市第七人民医院,上海200137

出　　处：《山东医药》2016年第11期14-17,共4页Shandong Medical Journal

基　　金：上海浦东新区卫计委课题(PW2013A-24);上海市第七人民医院人才培养计划项目(XX2013-001)

摘　　要：目的基于房颤患者细胞色素P450 2C9(CYP2C9)和维生素K环氧化物还原酶复合体1(VKORC1)基因型、年龄、身高建立华法林给药剂量计算公式,并进行评价。方法 122例房颤患者,应用聚合酶链反应-限制性片段长度多态性方法分析CYP2C9(rs1057910)和VKORC1(rs9923231)基因型,采用多元线性回归分析法依据CYP2C9和VKORC1基因型、年龄、身高建立华法林给药剂量计算公式。另选择60例房颤患者,随机分为对照组和实验组各30例。实验组按照华法林给药剂量计算公式的剂量给予,对照组给予华法林2.5 mg/d,均7 d,后根据国际标准化比值(INR)调整,直至达到稳定的华法林维持剂量,比较两组达到稳定的维持剂量所需的时间。结果华法林剂量=0.438-0.014 3×年龄+0.014 9×身高-0.324×CYP2C9×3+0.209×VKORC1,R2为0.564。实验组、对照组随访50 d,达到华法林维持剂量分别有26、19例,两组比较,P<0.05。实验组、对照组患者达到华法林维持剂量所需时间分别为(25.8±1.7)、(33.1±1.9)d,两组比较,P<0.05。结论建立了一个基于房颤患者CYP2C9和VKORC1基因型、年龄、身高的华法林给药剂量计算公式,根据该公式指导房颤患者的华法林治疗剂量能缩短达到华法林维持剂量所需的时间。Objective To develop and evaluate the warfarin-dosing algorithm based on cytochrome P450 2C9（ CYP2C9） and vitamin K epoxide reductase complex 1（ VKORC1） genotypes,age and height of patients with atrial fibrillation（ AF）. Methods A total of 122 AF patients were included and their genotypes of CYP2C9（ rs1057910） and VKORC1（ rs9923231） were analyzed by polymerase chain reaction-restriction fragment length polymorphism（ PCRRFLP）. Multiple linear regression was performed to develop a warfarin dosing algorithm which was based on age,height,CYP2C9 and VKORC1 genotypes of AF patients. Another 60 AF patients were enrolled and randomly assigned into the control group（ n = 30） and experimental group（ n = 30）. The experimental group received warfarin of ＂ predicted warfarin dose＂ based on warfarin dosing algorithm,and the control group received warfarin of 2. 5 mg / d. Both groups received warfarin for 7 days and then were adjusted to INR until reaching the stable warfarin maintenance dose. The time to reach a stable warfarin maintenance dose was compared between the control group and experimental group. Results The warfarin-dosing = 0. 438- 0. 014 3 × age ＋ 0. 014 9 × height-0. 324 × CYP2C9 × 3 ＋ 0. 209 × VKORC1,R^2= 0. 564. During the 50 day follow-up,there were 26 patients in the control group and 19 patients in the experimental group who acquired warfarin maintenance dose,with significant difference（ P〈0. 05）. The mean time from initiation to warfarin maintenance dose was significantly shorted in the experimental group（ 25. 8 ± 1. 7 d） than that in the control group（ 33. 1 ± 1. 9 d）,P〈0. 05.Conclusion A new warfarin-dosing algorithm is developed based on CYP2C9 and VKORC1 genotypes,age and height and it can shorten the time from initiation to warfarin maintenance dose in AF patients with warfarin therapy.

关 键 词：心房颤动 华法林 细胞色素P450 2C9 维生素K环氧化物还原酶复合体1 单核苷酸多态性 

分 类 号：R541.7[医药卫生—心血管疾病]