CYP2C9*3和VKORC1基因多态性对华法林预防骨科术后下肢深静脉血栓效果的影响  

Effects of CYP2C9*3 and VKORC1 gene polymorphisms on warfarin in prevention of deep venous thrombosis of lower limbs after orthopedic surgery

作　　者：王亮[1] 钟武[1] 

机构地区：[1]泸州医学院附属医院急诊科,泸州646000

出　　处：《上海交通大学学报（医学版）》2013年第10期1360-1363,1368,共5页Journal of Shanghai Jiao tong University:Medical Science

摘　　要：目的探讨CYP2C9*3和VKORC1-1639 G>A单核苷酸多态性对华法林(WRN)预防性治疗骨科手术后并发下肢深静脉血栓(DVT)效果的影响。方法以214例应用WRN预防下肢DVT风险的骨科手术后患者作为研究对象,采用聚合酶链式反应–限制性片段长度多态性(PCR-RFLP)分析法筛查CYP2C9*3和VKORC1-1639 G>A基因多态性,对基因多态性分布与WRN预防性治疗效果的关系进行统计学分析。结果 214例患者中CYP2C9*3的等位基因频率分别为94.9%和5.1%,VKORC1-1639 G>A中G和A突变的等位基因频率分别为10.5%和89.5%。CYP2C9*3基因中*1/*1、*1/*3和*3/*3基因型分布分别为90.7%、8.4%和0.9%,VKORC1-1639 G>A中GG、GA和AA基因型分布分别为0.9%、19.2%和79.9%。两者的频率分布均符合Hardy-Weinberg平衡。对术后WRN的个体稳定剂量按照基因多态性分布情况进行分组后发现,WRN稳定剂量与VKORC1-1639G>A和CYP2C9*3的基因多态性有关(P<0.01),且不同基因型携带者WRN治疗后DVT的发生率也不同。结论 VKORC1-1639 G>A和CYP2C9*3基因多态性可导致WRN预防患者骨科手术后DVT的稳定剂量改变,且与WRN的疗效有关。Objective To investigate the effects of CYP2C9 ＊ 3 and VKORCl-1639G 〉 A single nucleotide polymorphisms on warfarin （WFR） in prevention of deep venous thrombosis （DVT） of lower limbs after orthopedic surgery. Methods Two hundred and fourteen patients treated with WRN in prevention of DVT of lower limbs after orthopedic surgery were selected, the CYP2C9 ＊ 3 and VKORCI-1639G 〉 A polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） analysis, and the correlation of distribution of gene polymorphism with outcome of preventive treatment by WRN was statistically analysed. Results In these 214 patients, the frequencies of CYP2C9 ＊ 3 alleles were 94.9% and 5.1% respectively, and the frequencies of VKORCl-1639G 〉 A mutation in G and A alleles were 10. 5% and 89.5% respectively. The distributions of ＊ 1/＊ 1, ＊ 1/＊ 3 and ＊ 3/＊ 3 genotypes in CYP2C9 ＊ 3 gene were 90.7%, 8.4% and O. 9% respectively, and the distributions of GG, GA and AA genotypes in VKORCl-1639G 〉 A were 0.9%, 19.2% and 79.9% respectively. Both frequency distributions were in line with the Hardy-Weinberg equilibrium. Individual stable doses of WRN after operation were grouped based on the distributions of gene polymorphisms, and it was found that the stable doses of WRN were correlated with the gene polymorphisms of VKORCl-1639G 〉 A and CYP2C9 ＊ 3 （P 〈0. 01）. Besides, the incidences of DVT after WRN treatment varied among patients with different genotypes. Conclusion VKORCl-1639G 〉 A and CYP2C9 ＊ 3 polymorphisms may lead to the changes of stable doses of WRN in prevention of DVT of lower limbs after orthopedic surgery, and may be correlated to the clinical efficacy of WRN.

关 键 词：基因多态性 CYP2C9 VKORC1 骨科手术 血栓 静脉 

分 类 号：R543.6[医药卫生—心血管疾病]