环氧化物水解酶1基因多态性对华法林剂量影响的研究  

Effect of the Epoxide Hydrolase 1 Gene Polymerphism on Warfarin Dose

作　　者：罗万慰 张海燕[1] 马守梅 许联红[3] 张中行 杨协清[1] 

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心胸外科,江苏常州213002 [3]江苏大学附属武进医院中心实验室,江苏常州213002

出　　处：《中国药学杂志》2010年第19期1488-1491,共4页Chinese Pharmaceutical Journal

基　　金：常州四药临床药学科研基金项目(N0.CS2009901)

摘　　要：目的探讨苏南地区心脏机械瓣膜置换术后汉族人群环氧化物水解酶1(EPHX1)基因rs4653436和rs2292566多态性对华法林剂量的影响,为以后利用基因多态性指导临床合理用药提供理论依据。方法采用碱基淬灭探针技术,检测197名心脏机械瓣膜置换术后患者的EPHX1rs4653436和EPHX1rs2292566的基因型,分析对华法林剂量的影响。结果 EPHX1基因rs4653436多态性检测有127例纯合子GG型,62例患者为AG型杂合子,8例突变纯合子AA型;GG型患者华法林的平均稳定剂量为(2.64±0.93)mg.d-1,AG型为(2.52±0.68)mg.d-1,AA型为(3.25±1.63)mg.d-1,采用方差分析方法得到各组间华法林剂量差异P值大于0.05,无显著性差异;而EPHX1基因rs2292566多态性检测有107例纯合子GG型,70例AG型杂合子,20例突变纯合子AA型;GG型患者华法林的平均稳定剂量为(2.47±0.85)mg.d-1,AG型为(2.49±0.77)mg.d-1,AA型为(2.81±0.96)mg.d-1,方差分析方法得到各组间华法林剂量差异P值小于0.05,有显著性差异。结论在苏南地区心脏机械瓣膜置换术后汉族人群中,EPHX1基因rs4653436多态性与华法林剂量相关性无显著性差异,对华法林剂量影响较小;而rs2292566多态性与华法林剂量相关性有显著性差异,对华法林剂量有影响。OBJECTIVE To investigate the effect of EPHX1 rs4653436 and rs2292566 polymorphism on warfarin maintenance dose in the Han population. METHODSThe single nucleotide polymorphism was detected using base-quenched probe technique. EPHX1 rs4653436 and rs2292566 polymorphisms were analyzed in 197 patients with mechanical heart valve replacement. RESULTS The genotype of EPHX1 rs4653436 showed that 127 patients were homozygous GG ,62 were heterozygous AG,and 8 were homozygous AA genotype. Warfarin doses were （2.64±0.93） mg·d^-1 in patients with EPHX1 rs4653436 GG genotype,（2.52±0.68） mg·d^-1 in AG genotype,and （3.25±1.63）mg·d^-1 in AA genotype. ANOVA analysis showed EPHX1 rs4653436 showed no relationshiop with warfarin. However,the genotype of EPHX1 rs2292566 showed that 109 patients were homozygous GG ,70 were heterozygous AG,and 20 were homozygous AA genotype.Warfarin doses were （2.47±0.85） mg·d^-1 in patients with EPHX1 rs2292566 GG genotype,（2.49±0.77） mg·d^-1 in AG genotyp,and （2.81±0.96）mg·d^-1 in AA genotype. EPHX1 rs2292566 showed significant relationship with warfarin. CONCLUSION EPHX1 rs4653436 showed no relationship with the dose of warfarin ,yet,EPHX1 rs2292566 show significant relatiopship with warfarin dose in the Han population of south Jiangsu province.

关 键 词：环氧化物水解酶1 华法林 基因多态性 

分 类 号：R968.1[医药卫生—药理学]