CYP2C9*3和VKORC1基因多态性对苄丙酮香豆素钠治疗骨科术后下肢深静脉血栓的影响  

Effect of CYP2C9*3 and VKORC1 gene polymorphism on prevention of postoperative deep venous thrombosis by warfarin therapy 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,四川泸州646000

出　　处：《上海医学》2013年第9期767-771,共5页Shanghai Medical Journal

摘　　要：目的探讨CYP2C9*3和VKORC1-1639中G>A基因单核苷酸多态性对苄丙酮香豆素钠(WRN)治疗骨科术后并发下肢深静脉血栓(DVT)的影响。方法按计算机生成随机数的方法选取2008—2013年间在泸州医学院附属医院行骨科手术治疗的股骨骨折患者214例,均予WRN预防下肢DVT形成。采用聚合酶链反应限制性酶切方法(PCR-RFLP法)分析CYP2C9*3和VKORC1-1639G>A基因多态性,将VKORC1-1639G>A 3种基因型与CYP2C9*3 3种基因型进行组合,记录各基因型患者的最终WRN稳定剂量,以及术后3个月随访时各组DVT的发生率。结果 214例患者均存在VKORC1-1639中A>G基因多态性,VKORC1-1639G>A中GG、GA、AA型的比例分别为0.9%(2/214)、19.2%(41/214)、79.9%(171/214),VKORC1-1639G突变基因频率为10.3%(22/214);存在CYP2C9中*1/*3基因多态性,CYP2C9*3基因*1/*1、*1/*3和*3/*3型的比例分别为90.7%(194/214)、8.4%(18/214)、0.9%(2/214),CYP2C9*3的突变基因频率为5.1%(11/214)。经Hardy-Weinberg遗传平衡定律检验,VKORC1-1639中G>A和CYP2C9中*1/*3位点基因多态性的分布均符合遗传平衡。携带VKORC1-1639GG基因型的患者服用WRN的稳定剂量为(5.89±1.22)mg/d,显著高于VKORC1-1639GA和AA基因型的(4.26±1.12)和(2.84±0.65)mg/d(P值均<0.05)。携带CYP2C9*1/*1基因型的患者服用WRN的稳定剂量为(3.21±1.05)mg/d,显著高于CYP2C9*1/*3和*3/*3基因型的(2.23±0.46)和(1.23±0.48)mg/d(P值均<0.05)。将VKORC1-1639G>A 3种基因型与CYP2C9*3 3种基因型进行组合,得到GG&*1/*1、GA&*1/*1、AA&*1/*1、GA&*1/*3、AA&*1/*3、GA&*3/*3和AA&*3/*3 7种组合基因型。携带AA&*1/*1基因型154例、GA&*1/*1基因型38例、AA&*1/*3基因型16例、GG&*1/*1基因型2例、GA&*1/*3基因型2例、GA&*3/*3基因型1例和AA&*3/*3基因型1例,WRN的稳定剂量分别为(2.96±0.95)、(4.46±1.63)、(2.08±0.48)、(5.89±1.22)、(3.09±0.47)、1.57和0.89mg/d。GG&*1/*1、GA&*1/*1、AA&*1/*1、GA&*1/*3、AA&*1/*3、GA&*3/*3和AA&*3/*3型患者术后3个月随访时DVT发�Objective To investigate the effect of CYP2C9 ＊ 3 and VKORO1-1639G〉A single nucleotide polymorphism on the prevention of deep venous thrombosis （DVT） by warfarin after orthopedic surgery. Methods According to random choice method on computer, a total of 214 patients treated in the department of traumatic orthopedics of our hospital from year 2008 to 2013 were enrolled in this study. All the patients were given warfarin to prevent DVT. CYP2C9 ＊ 3 and VKORCl-1639G〉A polymorphism was analyzed by polymerase chain reactionrestriction fragment length polymorphism（POR-RFLP） method. Three genotypes of VKORC1-1639G〉A and three genotypes of CYP2C9 ＊ 3 were combined. The stable dose of warfarin in patients with different genotypes and the incidence of DVT 3 months after surgery were recorded. Results VKORC1-1639G〉A in the GG, GA and AA population distribution were 0.9% （2/214）, 19.2% （41/214） and 79.9% （171/214）. Mutant gene frequency of VKORC1-1639G〉A was 10.5%. Genes CYP2C9 ＊ 3 ＊ 1/＊ 1, ＊ 1/＊ 3 and ＊ 3/＊ 3 population distribution were 90.7 % （ 194/214）, 8.4 % （ 18/214） and 0.9 % （2/214）, respectively. Mutant gene frequency of CYP2C9 ＊ 3 was 5.1%. Both VKORC1-1639 G〉A and CYP2C9 ＊ 1/＊ 3 were in line with the frequency distribution of HardyWeinberg equilibrium. The stable dose of warfarin in the patients with VKORCl-1639GG was （5.89 ± 1.22） mg/d, which was significantly higher than that in the patients with VKORC1-1639GA and VKORC1-1639AA （[4.26±1. 121 mg/d, 1-2.84 ± 0. 651 mg/d, both P〈0.05）. The stable dose of warfarin in the patients with CYP2C9 ＊ 1/ ＊ 1 was （3.21 ± 1.05） mg/d, which was significantly higher than that in the patients with CYP2C9 ＊ 1/＊ 3 and CYP2C9＊3/＊3 （[2.23±0.46]mg/d, [1.23±0.48]mg/d, both P〈0.05）. After combination of VKORC1- 1639G〉A and CYP2C9 ＊ 3, we obtained seven genotypes-GG＆ ＊ 1/＊ 1, GA＆ ＊ 1/＊ 1, AA＆ ＊ 1/＊ 1, GA＆ 1/＊ 3, AA＆ ＊ 1/＊ 3, GA＆ ＊ 3/＊ 3 and AA

关 键 词：基因多态性 CYP2C9 VKORC1 老年 心血管 血栓 静脉 

分 类 号：R543.6[医药卫生—心血管疾病]