脑卒中患者氯吡格雷抵抗与CYP2C19基因多态性和 P2Y12受体的相关性研究  

Correlation study between clopidogrel resistance and CYP2C19 gene polymorphism,P2Y12 receptor in stroke patients

作　　者：杜安妮 林牧[2] 蔡锐 DU Anni;LIN Mu;CAI Rui(Department of Pharmacology,Zunyi Medical College,Zunyi,Guizhou 563000,China;Central Laboratory,Guizhou Aerospace Hospital,Zunyi,Guizhou 563000,China;People′s Hospital of Honghuagang District of Zunyi,Zunyi,Guizhou 563000,China)

机构地区：[1]遵义医药高等专科学校药理教研室,贵州遵义563000 [2]贵州航天医院中心实验室,贵州遵义563000 [3]遵义市红花岗区人民医院,贵州遵义563000

出　　处：《现代医药卫生》2023年第3期419-424,共6页Journal of Modern Medicine & Health

基　　金：贵州省遵义市科技局资助项目(遵市科合社字[2018]50号)。

摘　　要：目的研究脑卒中患者氯吡格雷抵抗与CYP2C19基因多态性和P2Y12受体之间相关性。方法选取2019年1月至2020年12月于贵州航天医院住院、临床诊断为缺血性脑卒中患者298例,在服用氯吡格雷前检测其CYP2C19、P2Y12基因分型,从中筛选出CYP2C19*2(GA型+AA型)患者,观察其P2Y12不同基因位点C34T、G52T、i-T774C在用药前及用药7 d后血小板聚集率的差值比较,分析相关性。结果CYP2C19*1/*1基因型患者占比最高(39.9%),CYP2C19*3/*3及CYP2C19*1/*17基因型患者占比最低(均为0.3%),其中UM型4例(1.3%),EM型119例(39.9%),IM型133例(44.7%),PM型42例(14.1%)。CYP2C19*2患者中P2Y12基因多态性C34T位点组CC型83例(56.5%),CT型56例(38.1%),TT型8例(5.4%),G52T位点组GG型91例(62.8%),GT型48例(33.1%),TT型6例(4.1%);服用氯吡格雷前后各基因间血小板聚集率差值比较,差异均无统计学意义(P>0.05)。CYP2C19*2患者中P2Y12基因多态性i-T744C位点组TT型78例(52.7%),TC型60例(40.5%),CC型10例(6.8%),服用氯吡格雷前后各基因间血小板聚集率差值比较,差异有统计学意义(P<0.05)。结论脑卒中患者基因分布情况以EM和IM型为主,P2Y12受体中C34T、G52T位点可能与氯吡格雷抗血小板作用无明显相关性,i-T744C位点与血小板活性有相关性,可能是导致脑卒中患者氯吡格雷抵抗的原因之一。Objective To investigate the correlation between clopidogrel resistance and CYP2C19 gene polymorphism, P2Y12 receptor in stroke patients.Methods A total of 298 patients hospitalized in Guizhou Aerospace Hospital and clinically diagnosed as ischemic stroke from January 2019 to December 2020 were selected.The genotypes of CYP2C19 and P2Y12 were detected before taking clopidogrel, and the patients with CYP2C19*2(GA+AA type) were selected.The differentials of platelet aggregation rates of different P2Y12 gene loci C34T,G52T and i-T774C before and seven days after taking clopidogrel were observed, and the correlation was analyzed.Results CYP2C19*1/*1 genotype patients accounted for the highest proportion(39.9%),CYP2C19*3/*3 and CYP2C19*1/*17 genotype patients accounted for the lowest proportion(all 0.3%),including four cases of UM type(1.3%),119 cases of EM type(39.9%),133 cases of IM type(44.7%) and 42 cases of PM type(14.1%).In the P2Y12 gene polymorphism C34T locus group in CYP2C19*2 patients, there were 83 cases of CC type(56.5%),56 cases of CT type(38.1%) and 8 cases of TT type(5.4%).In the G52T locus group, there were 91 cases of GG type(62.8%),48 cases of GT type(33.1%) and 6 cases of TT type(4.1%).There was no significant difference in platelet aggregation rate between genes before and after taking clopidogrel(P>0.05).In the P2Y12 gene polymorphism i-T744C locus group in CYP2C19*2 patients, there were 78 cases of TT type(52.7%),60 cases of TC type(40.5%),and 10 cases CC type(6.8%).The difference in platelet aggregation rate between genes before and after taking clopidogrel was statistically significant(P<0.05).Conclusion The gene distribution of stroke patients is dominated by EM and IM types.The C34T and G52T locus in the P2Y12 receptor may not be significantly related to the antiplatelet effect of clopidogrel.The i-T774C locus is associated with platelet activity, which may be among the causes of clopidogrel resistance in stroke patients.

关 键 词：氯吡格雷抵抗 CYP2C19 P2Y12受体 基因多态性 缺血性脑卒中 

分 类 号：R966[医药卫生—药理学] Q786[医药卫生—药学]