VKORC1、CYP2C9、CYP4F2、EPHX1基因多态性对华法林剂量的影响  

Influence of VKORC1,CYP2C9,CYP4F2 and EPHX1 Gene Polymorphisms on Warfarin Dose

作　　者：张海燕[1] 罗万慰 方焕荣[1] 杨协清[1] 许联红[2] 马守梅 

机构地区：[1]江苏大学附属武进医院药剂科,江苏常州213002 [2]江苏大学附属武进医院检验科,江苏常州213002 [3]江苏大学附属武进医院心胸外科,江苏常州213002

出　　处：《中国药房》2012年第34期3201-3205,共5页China Pharmacy

基　　金：江苏省卫生厅医学科技发展基金(P200804);常州四药提供临床药学科研项目的基金资助

摘　　要：目的:探讨中国汉族人群VKORC1、CYP2C9、CYP4F2和EPHX1基因多态性对华法林剂量的影响。方法:采用限制性片段多态性技术和碱基淬灭探针技术检测197名心脏机械瓣膜置换术后患者的VKO RC1-1639G>A、CYP2C9 1075A>C、CYP4F2 rs2108622和EPHX1 rs2292566的基因多态性,结合患者的临床特征,分析各因素对华法林剂量的影响。结果:VKO RC1-1639G>A、CYP2C9 1075A>C、CYP4F2 rs2108622、EPHX1 rs2292566基因多态性以及体重和年龄分别解释了30.2%、7.0%、2.8%、3.6%、1.9%和1.7%的华法林个体剂量差异,多因素联合可解释46.7%的华法林个体剂量差异。结论:VKORC1-1639G>A和CYP2C9 1075A>C基因多态性是影响华法林稳定剂量重要的遗传因素;CYP4F2 rs2108622和EPHX1 rs2292566基因多态性以及年龄、体重对华法林的稳定剂量有影响,但较小。OBJECTIVE： To investigate the influence of VKORC1, CYP2C9, CYP4F2 and EPHX1 gene polymorphisms on warfarin dose in the Han population. METHODS： The gene polymorphisms of VKORCl-1639G〉A, CYP2C9 1075A〉C, CYP4F2 rs2108622 and EPHX1 rs2292566 in 197 patients with mechanical heart valve replacement were detected by using base-quenched probe technique and PCR-RFLP technique. The iufluence of factors on warfariu dose was analyzed on the basis of clinical character- istics of patients. RESULTS： The gene polymorphisms of VKORCl-1639G〉A, CYP2C9 1075A〉C, CYP4U2 rs2108622 and EPHX1 rs2292566, weight and age demonstrated 30.2%, 7.0%, 2.8%, 3.6%, 1.9% and 1.7% of warfarin dose variance, respec- tively, and multiple factors combination demonstrated totally 46.7%. CONCLUSION： The gene polymorphisms of VKORCl-1639G〉A and CYP2C9 1075A〉C are significant hereditary factors influencing warfarin dose. However, age, weight and the gene polymorphisms of CYP4F2 rs2108622, EPHX1 rs2292566 have little influences on warfarin dose.

关 键 词：维生素K环氧化物还原酶亚单位1 细胞色素P450 酶2C9 细胞色素P450酶4F2 环氧化物水解酶1 华法林 基因多态性 

分 类 号：R973.2[医药卫生—药品] R969.3[医药卫生—药学]