CYP2C19基因多态性与氯吡格雷预防缺血性脑卒中复发的临床相关性研究  

Clinical Correlation between CYP2C19 Gene Polymorphism and Clopidogrel Preventing Recurrence of Ischemic Stroke

作　　者：严洁萍[1] 陈波[2] 郑水莲[1] 胡颖[1] 张夙[1] 晁健 蒋燕青 杨秀丽[1] 黄萍 Yan Jieping;Chen Bo;Zheng Shuilian;Hu Ying;Zhang Su;Chao Jian;Jiang Yanqing;Yang Xiuli;Huang Ping(Department of Pharmacy,Zhejiang Provincial People’s Hospital,People’s Hospital of Hangzhou Medical College,Hangzhou 310014,China;Department of Neurology,Zhejiang Provincial People’s Hospital,People’s Hospital of Hangzhou Medical College;Department of Electrocardiograph,Ningbo Medical Center Lihuili Eastern Hospital;Departmeat of Pharmacy,People’s Hospital of Xianju County)

机构地区：[1]浙江省人民医院,杭州医学院附属人民医院药学部,杭州310014 [2]浙江省人民医院,杭州医学院附属人民医院神经内科 [3]宁波市医疗中心李惠利东部医院心电图室 [4]浙江省仙居县人民医院药剂科

出　　处：《中国药师》2020年第7期1355-1358,共4页China Pharmacist

基　　金：国家自然科学基金项目(编号:81903597);浙江省自然科学基金项目(编号:LQ16H310003);浙江省药学会药学专项科研项目(编号:2016ZYY14);浙江省医药卫生科技计划项目(编号:2019316359、2015KYB036);浙江省中医药科学研究项目(编号:2015ZB009)。

摘　　要：目的:探讨CYP2C19基因多样性(*2,*3,*17位点)与氯吡格雷预防缺血性脑卒中(CIS)复发临床疗效的相关性,根据血栓弹力图的结果以及基因检测结果,合理指导临床个体化用药。方法:收集2017年1月~2018年6月浙江省人民医院神经内科的CIS患者,分别检测CYP2C19*2、*3和*17等位基因突变类型。患者连续服用氯吡格雷7 d后,于第8天抽静脉血,2 h内完成血栓弹力图血小板图检测,根据血小板抑制率分析氯吡格雷疗效,随访1年CIS患者的复发及不良反应。结果:共纳入109例CIS患者,其中超快代谢型4例(3.67%),平均ADP抑制率为(57.23±15.35)%,12个月再发缺血事件为0;快代谢型64例(58.72%),平均ADP抑制率为(51.86±25.06)%,12个月再发缺血事件8例次(12.50%);中代谢型37例(33.94%),平均ADP抑制率为(48.34±22.42)%,12个月再发缺血事件7例次(18.92%);慢代谢型4例(3.67%),平均ADP抑制率为(30.22±17.08)%,12个月再发缺血事件为0。1例快代谢型患者出现颅内外出血,其他基因型均未出现。消化道不良反应:超快代谢型2例(50%),快代谢型5例(7.81%),中代谢型1例(2.70%),慢代谢型1例(25%)。不同基因型患者均无死亡病例。结论:CYP2C19基因多态性与氯吡格雷预防CIS复发密切相关。与超快代谢型、快代谢型相比,慢代谢型ADP抑制率显著降低;而CYP2C19*17等位基因增加患者消化道不良反应。Objective:To investigate the relationship between CYP2 C19 gene diversity(*2,*3 and*17)and the recurrence prevention efficacy of clopidogrel on cerebral ischemic stroke,and according to the results of thromboelastography and genetic testing,to guide rational individualized application of drugs in clinics.Methods:The patients with ischemic stroke admitted to the Department of Neurology,Zhejiang Provincial People’s Hospital from January 1 st 2017 to June 30 th 2018 were randomly selected.Seven days after oral administration of clopidogrel,venous blood was withdrawn on the morning of the 8 th day,and the thromboelastogram platelet map was completed within 2 hours.The efficacy of clopidogrel was analyzed according to the platelet inhibition rate,and the clinical use of chlorine was attempted.Results:A total of 109 CIS patients were enrolled in the study.Totally 4 patients(3.67%)were in ultra-fast metabolic type with the average ADP inhibition rate of(57.23±15.35)%and the recurrence of ischemic events in 12 months of zero.Totally 64 patients(58.72%)were in fast metabolic type with the average ADP inhibition rate of(51.86±25.06)%and the recurrence of ischemic events in 12 months of 8 cases(12.50%).Totally 37 patients(33.94%)were in medium metabolic type with the average ADP inhibition rate of(48.34±22.42)%and the recurrence of ischemic events in 12 months of 7 cases(18.92%).Totally 4 patients(3.67%)were in slow metabolic type with the average ADP inhibition rate of(30.22±17.08)%and the recurrence of ischemic events in 12 months of zero.In terms of adverse drug reactions,CYP2 C19 gene polymorphism was associated with intracranial and extracranial hemorrhage.Only one case of EM had intracranial and extracranial hemorrhage,and the other genotypes were all zero.In the aspect of gastrointestinal adverse reactions,there were 2 cases(50%)in ultra-fast metabolic type,5 cases(7.81%)in fast metabolic type,one case(2.70%)in medium metabolic type and one case(25%)in slow metabolic type.There were no deaths among different ge

关 键 词：氯吡格雷 缺血性脑卒中 CYP2C19基因多态性 血小板抑制率 

分 类 号：R968[医药卫生—药理学] R973.2[医药卫生—药学]