2021 年12 期 第29 卷
用药指导CYP2C9和VKORC1基因多态性对华法林个体化用药的指导价值
Guiding Value of Genetic Polymorphisms in CYP2C9 and VKORC1 for the Individualized Medication of Warfarin
作者:丁维剑,汪亚南,苗仁华
- 单位:
- 238000 安徽省巢湖市,安徽医科大学附属巢湖医院药剂科 通信作者:丁维剑,E-mail:dingweijian09@163.com
- Units:
- Pharmacy Department, Chaohu Hospital Affiliated to Anhui Medical University, Chaohu 238000, China Corresponding author: DING Weijian, E-mail: dingweijian09@163.com
- 关键词:
- 抗凝药; 华法林; CYP2C9基因; VKORC1基因; 多态性,单核苷酸; 个体化用药;
- Keywords:
- Anticoagulants; Warfarin; CYP2C9 gene; VKORC1 gene; Polymorphism, single nucleotide; Personalizedmedication
- CLC:
- DOI:
- 10.12114/j.issn.1008-5971.2021.00.291
- Funds:
摘要:
背景华法林是目前临床上使用广泛、效果确切的抗凝药,但其治疗时间窗较窄、个体差异较大,故提高华法林个体化用药的合理性具有重要的临床意义。目的 分析CYP2C9和VKORC1基因多态性对华法林个体化用药的指导价值。方法 收集2020年6月至2021年6月在安徽医科大学附属巢湖医院药剂科治疗药物监测实验室进行CYP2C9*3和VKORC1-1639G>A位点基因多态性检测的住院患者54例,均为汉族人群。记录患者CYP2C9*3和VKORC1-1639G>A位点基因多态性;参照华法林剂量公益网站计算出的华法林推荐剂量,比较华法林使用剂量为推荐剂量者与华法林使用剂量为非推荐剂量者华法林治疗2~3 d后国际标准化比值(INR)达标率。结果 54例患者中华法林治疗2~3 d后检测INR者23例,CYP2C9*3和VKORC1-1639G>A位点基因多态性:AA/AA基因型18例(占78.3%),AA/GA基因型3例(占13.0%),AC/AA基因型1例(占4.3%)、AA/GG基因型1例(占4.3%)。23例患者中华法林使用剂量为推荐剂量者11例,华法林使用剂量为非推荐剂量者12例;华法林使用剂量为推荐剂量者华法林治疗2~3 d后INR达标率高于华法林使用剂量为非推荐剂量者(P <0.001)。结论 按照CYP2C9*3和VKORC1-1639G>A位点基因多态性推荐华法林用药剂量可使患者INR尽快达标,进而提高华法林抗凝效果及用药合理性。
Abstract:
【Abstract】 Background Warfarin is currently a widely used anticoagulant drug with definite efficacy in clinicalpractice. Due to the narrow treatment window and large individual differences, it is of great clinical significance to improve therationality of warfarin individualized medication. Objective To analyze the guiding value of genetic polymorphisms in CYP2C9and VKORC1 for the individualized medication of warfarin. Methods A total of 54 inpatients undergoing CYP2C9*3 andVKORC1-1639G > A gene polymorphisms detected in the Therapeutic Drug Monitoring Laboratory of the Pharmacy Departmentof Chaohu Hospital Affiliated to Anhui Medical University from June 2020 to June 2021 were collected, they were Han population.CYP2C9*3 and VKORC1-1639G>A gene polymorphisms were recorded; with reference to the recommended dose of warfarincalculated by the warfarin dose public welfare website, the international standardized ratio (INR) compliance rate at 2-3 daysafter warfarin treatment were compared between patients received the recommended dose of warfarin and patients received the nonrecommended dose of warfarin. Results In 54 patients, the INR was detected in 23 patients at 2-3 days after warfarin treatment.CYP2C9*3 and VKORC1-1639G>A gene polymorphism distribution: AA/AA genotype in 18 cases (78.3%) , AA/GA genotype in3 cases (13.0%) , AC/AA genotype in 1 case (4.3%) and AA/GG genotype in 1 case (4.3%) . In 23 patients, 11 patients receivedthe recommended dose of warfarin and 12 patients received the non recommended dose of warfarin; the INR compliance rate at2-3 days after warfarin treatment of patients received recommended dose of warfarin was higher than that of patients received nonrecommended dose of warfarin (P < 0.001) . Conclusion According to CYP2C9*3 and VKORC1-1639G>A gene polymorphism,the recommended dosage of warfarin can make the INR of patients reach the standard as soon as possible, so as to improve theanticoagulant effect and medication rationality of warfarin.
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