设为首页 |  加入收藏
首页期刊介绍编委会投稿须知通知公告刊登文章继续教育园地协办单位联系我们广告合作
公告栏:
CYP2C19和ABCB1基因检测指导患者氯吡格雷个体化给药
作者:郭秀彩1  银雪艳1  许启荣1  李云波2  张紫萍1 
单位:1. 广州市第十二人民医院, 广东 广州 510620;
2. 佛山市第一人民医院同济康复医院, 广东 佛山 528000
关键词:CYP2C19 ABCB1 氯吡格雷 个体化给药 
中图分类号:R743.3
文献标志码:
出版年,卷(期):页码:2020,30(1):36-39,
收稿日期:2019-8-1
摘要:
目的 利用CYP2C19ABCB1基因检测结果指导患者氯吡格雷个体化用药。方法 选取某院2018年8月~2019年6月30例使用氯吡格雷的患者,采用荧光原位杂交法检测患者氯吡格雷相关基因(CYP2C19*17、CYP2C19*3CYP2C19*2ABCB1)的基因型,根据检测结果为患者提供给药建议。另选取1例冠状动脉粥样硬化心脏病PCI术后患者,测定氯吡格雷相关基因型,为患者提供个体化给药建议。结果 CYP2C19基因检测结果显示,30例患者中1例为超快代谢型,8例为快代谢型,18例为中间代谢型,3例为慢代谢型; ABCB1 CC野生型13例,CT突变杂合型14例,TT突变纯合型3例。1例冠状动脉粥样硬化心脏病患者PCI术后规律双联抗血小板治疗仍反复胸闷胸痛,CYP2C19基因检测为CYP2C19*1/*2中间代谢型,无ABCB1突变,药物代谢减慢,建议氯吡格雷更换为替格瑞洛。结论 通过基因检测指导患者氯吡格雷个体化给药,促进临床合理用药。
OBJECTIVE To utilize CYP2C19 and ABCB1 gene testing so as to guide individualized administration of clopidogrel in patients. METHODS Totally 30 patients who received clopidogrel from August 2018 to June 2019 in oua hospital were selected, and the genotypes of clopidogrel-related genes (CYP2C19*17, CYP2C19*3, CYP2C19*2 and ABCB1) were detected by Fluorescence in situ hybridization, and the recommendations were provided for the patients according to genotype. A patient with coronary heart disease after PCI was collected, the genotypes of clopidogrel-related genes were determined.The suggestions about individualized anti-platelet therapy were provided for patients. RESULTS Among 30 patients, the testing result of CYP2C19 showed that 1 person was ultrarapid metabolizer, 8 persons were extensive metabolizers, 18 persons were intermediate metabolizers, and 3 persons were poor metabolizers. The testing result of ABCB1 showed that 13 persons had wild type of CC, 14 persons had mutant heterozygous type of CT, and 3 persons had mutation homozygous type of TT. A patient with coronary heart disease after PCI was still feeling chest tightness and chest pain, which received standard dual antiplatelet therapy, CYP2C19 was CYP2C19*1/*2 intermediate metabolizer, without ABCB1 mutation. It was recommended that clopidogrel should be replaced with ticagrelor by the slowing down of drug metabolism. CONCLUSION Gene detection guide individualized administration of clopidogrel in patients so as to promote clinical rational drug use.
基金项目:
广东省医院药学研究基金(2018JZ02)
作者简介:
郭秀彩,主管药师,Tel:020-38665683,E-mail:406044730@qq.com
通讯作者:张紫萍,主任药师,Tel:020-38665695,E-mail:zzp08@126.com
参考文献:
[1] Smith S C, Feldman T E,Hirshfeld J W,et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention:a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention)[J].J Am Coll Cardiol,2006,47(1):e1-e121.
[2] Aradi D,Komócsi A,Vorobcsuk A,et al.Impact of clopidogrel and potent P2Y12-inhibitors on mortality and stroke in patients with acute coronary syndrome or undergoing percutaneous coronary intervention:a systematic review and meta-analysis[J].Thromb Haemost 2013,109(1):93-101.
[3] Nguyen T A,Diodati J G,Pharand C.Resistance to clopidogrel: a review of the evidence[J].J Am Coll Cardiol,2005,45(8):1157-1164.
[4] 付梦璐,董若兰,凃玲,等.氯吡格雷抵抗研究进展[J].医药导报,2018,37(2):139-145.
[5] 吴天源,李韶南,罗义,等.急性冠脉综合征患者氯吡格雷抵抗与平均血小板体积及预后的相关性[J].岭南心血管病杂志,2018,24(5):502-505,510.
[6] Taubert D,Von B N,Grimberg G,et al. Impact of P-glycoprotein on clopidogrel absorption[J]. Clin Pharmacol Ther,2006,80(5):486-501.
[7] Kazui M,Nishiya Y,Ishizuka T,et al.Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite[J].Drug Metab Dispos,2010,38(1):92-99.
[8] Scott S A,Sangkuhl K,Gardner E E,et al.Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450-2C19(CYP2C19) Genotype and Clopidogrel Therapy[J].Clinical pharmacology and therapeutics,2011,90(2):328-332.
[9] Savi P,Herbert J M.Clopidogrel and ticlopidine:P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis[J].Semin Thromb Hemost,2005,31(2):174-183.
[10] Holmes D R,Dehmer G J,Kaul S,et al.ACCF /AHA clopidogrel clinical alert: approaches to the FDA "boxed warning":a report of the American College of Cardiology Foundation Task Force on clinical expert consensus documents and the American Heart Association endorsed by the Society for Cardiovas[J].J Am Coll Cardiol,2010,56(4):321-341.
[11] 肖飞燕, 张伟, 周宏灏, 等. 影响氯吡格雷疗效的基因多态性研究进展[J].中国现代应用药学, 2016, 33(3):375-380.
[12] Simon T,Verstuyft C,Mary-Krause M,et al.Genetic determinants of response to clopidogrel and cardiovascular events[J].N Engl J Med,2009,360(4):363-375.
[13] Moriya Y,Nakamura T,Horinouchi M,et al.Effects of polymorphisms of MDR1,MRP1,and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects[J].Bio Pharm Bull,2002,25(10):1356-1359.
[14] Chen D Y,Wang C Y,Wen M S,et al. Paraoxonase-1 is not a major determinant of stent thrombosis in a Taiwanese population[J]. PLoS One,2012,7(6):e39178.
[15] 梁欣,陈世财,夏彬彬,等.细胞色素P4502C19、PON1及ABCB1基因多态性与氯吡格雷抵抗的关联分析[J].中国临床药理学杂志,2017,33(7):585-588.
[16] Tatarunas V,Kupstyte N,Giedraitiene A,et al.The impact of CYP2C19*2,CYP4F2*3,and clinical factors on platelet aggregation,CYP4F2 enzyme activity,and 20-hydroxyeicosatetraenoic acid concentration in patients treated with dual antiplatelet therapy[J].Blood Coagul Fibrinolysis,2017,28(8):658-664.
[17] Mega J L,Simon T,Collet J P,et al.Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI:A Meta-Analysis[J].Jama,2010,304(16):1821-1830.
[18] Roberts J D,Wells G A,Le M M R,et al.Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE):a prospective,randomised,proof-of-concept trial[J].Lancet,2012,379(9827):1705-1711.
[19] Wei W,Fang L,Wang N,et al.Prevalence of CYP2C19 polymorphisms involved in clopidogrel metabolism in Fejian Hart populatio[J].Chin J Med Genet,2012,29(4):420-425.
服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
 
友情链接  
广东今日药学杂志社有限公司   地址:广州市东风东路753号东塔7楼702
电话:020-37886325       邮箱:jinriyaoxue@163.com
本系统由北京博思汇文数字科技有限公司设计开发 技术服务电话:400-921-9838
粤ICP备20054928号

粤公网安备 44010402002138号

您是第 165444 位访问者