CYP2C9和VKORC1基因多态性对华法林抗凝强度的影响

发布时间：2018-01-29 19:19

本文关键词： 华法林基因多态性 VKORC CYPC 血药浓度　出处：《第二军医大学学报》2016年05期 　论文类型：期刊论文

【摘要】：目的探讨上海地区汉族人群中细胞色素氧化酶P450 2C9(CYP2C9)、维生素K环氧化物还原酶复合体1(VKORC1)基因多态性对华法林稳定剂量及华法林血浆浓度的影响。方法纳入在体外循环下行瓣膜置换术且术后需服用华法林抗凝的患者226例,采用焦磷酸测序及UPLC/MS-MS法分别检测其CYP2C9和VKORC1基因型及其华法林血浆总浓度及游离浓度,分别以基因型、性别、年龄进行分组,比较不同组别患者华法林维持剂量和血浆浓度,并计算基因多态性及血药浓度、性别、年龄对华法林稳定剂量的贡献率。结果 CYP2C9(1061A/C)基因型中,AA型患者华法林维持量高于AC型(P0.05);VKORC1(-1639G/A)基因型中,AG型患者华法林维持量高于AA型患者(P0.01);VKORC1(1173C/T)基因型中,CT型患者华法林维持量高于TT型患者(P0.01)。CYP2C9(1061A/C)不同基因型间其华法林血浆浓度差异无统计学意义,VKORC1(-1639G/A)不同基因型间及VKORC1(1173C/T)不同基因型间华法林血浆浓度差异有统计学意义(P0.01)。男性患者所需华法林维持量高于女性患者(P0.05),60岁以上患者所需华法林维持量低于60岁以下患者(P0.05)。CYP2C9(1061A/C)、VKORC1(-1639G/A)、VKORC1(1173C/T)基因多态性及华法林血药浓度、年龄、性别分别解释了7.2%、29.1%、30.4%、6.7%、1.6%和1.4%的华法林个体剂量差异,多因素联合可解释47.2%的华法林个体剂量差异。结论 CYP2C9基因多态性与华法林抗凝药物剂量的个体间差异有关;VKORC1基因多态性与华法林抗凝药物剂量的个体间差异有关,且与其血药浓度密切相关。年龄和性别是影响华法林维持量的重要非基因因素。
[Abstract]:Objective to study the cytochrome oxidase P450 2C9 (CYP2C9) in the Han population of Shanghai. Vitamin K epoxide reductase complex 1 (VKORC1). Effect of gene polymorphism on warfarin stabilizer dosage and warfarin plasma concentration. Methods 226 patients with valvular replacement underwent cardiopulmonary bypass and received warfarin anticoagulant. The total plasma concentration and free concentration of warfarin and CYP2C9 and VKORC1 genotypes were detected by pyrosequencing and UPLC/MS-MS respectively. Age groups were used to compare the maintenance dose and plasma concentration of warfarin in different groups of patients, and to calculate the gene polymorphism, blood drug concentration and sex. Results the maintenance rate of warfarin in CYP2C9 1061A / C genotype was higher than that in AC genotype (P 0.05). The maintenance of warfarin in VKORC1-1639G / A genotype was higher than that in AA genotype. In the VKORC1 / 1173C / T genotype. The maintenance level of warfarin in CT patients was higher than that in TT patients (P 0.01). There was no significant difference in plasma concentrations of warfarin among different genotypes (CYP2C9 1061A / C). The plasma concentrations of warfarin were significantly different among different genotypes of VKORC1- 1639G / A and between different genotypes of VKORC1 and 1173C / T (P0.01). The maintenance of warfarin in male patients was higher than that in female patients (P 0.05). The maintenance of warfarin in patients over 60 years of age was lower than that in patients under 60 years of age (P0.05N. CYP2C9 1061A / C / VKORC1- 1639G / A.). The polymorphism of VKORC1 / 1173C / T gene and warfarin concentration, age and sex explained 7.2and 29.1C / T, respectively. The individual doses of warfarin in 1.6% and 1.4% were different. Multivariate association can explain the individual dose difference of warfarin in 47.2%. Conclusion the polymorphism of CYP2C9 gene is related to the individual difference of warfarin anticoagulant dosage. The polymorphism of VKORC1 gene is related to the individual difference of warfarin anticoagulant dosage, and it is closely related to the concentration of warfarin. Age and sex are the important non-gene factors that influence the maintenance of warfarin.
【作者单位】：第二军医大学长征医院胸心外科;第二军医大学长征医院药材科;
【基金】：上海市优秀学科带头人计划(12XD1400300) 上海市卫生与计划生育委员会青年项目(2012Y137)~~
【分类号】：R969
【正文快照】： [Acad J Sec Mil Med Univ,2016,37(5):640-644]华法林(warfarin)是常用的口服抗凝药,多用于人工瓣膜置换、血栓栓塞性疾病及房颤等的抗凝治疗[1]。由于华法林的治疗窗较窄,在临床使用过程中不同个体间的稳定治疗剂量有着较大的差异,若剂量不足将导致血栓栓塞,而剂量过大则有

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