细胞色素P4502C19基因多态性及代谢型与ADP诱导的血小板聚集抑制率及氯吡格雷抵抗的关联性研究  

Correlation study between cytochrome P4502C19 gene polymorphism or metabolic type and ADP induced-platelet aggregation inhibition and clopidogrel resistance

作　　者：彭静 刘俊[1] 许慧芳 李越然 江佳[1] 汪盛 周德喜[1] 朱艳虹[1] 杨魁 栾家杰[1] PENG Jing;LIU Jun;XU Huifang;LI Yueran;JIANG Jia;WANG Sheng;ZHOU Dexi;ZHU Yanhong;YANG Kui;LUAN Jiajie(Department of Pharmacy,Yijishan Hospital of Wannan Medical College,Wuhu 241001,Anhui,China)

机构地区：[1]皖南医学院弋矶山医院药学部,安徽芜湖241001

出　　处：《中国临床药理学与治疗学》2020年第7期746-751,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省科技攻关项目(1604a0802097);皖南医学院中青年项目自然科学类(WK2016F10,WK2017F14,WK2018F09);皖南医学院弋矶山医院三新项目(Y1604)。

摘　　要：目的:探讨细胞色素P450(CYP)2C19基因多态性及代谢型对二磷酸腺苷(ADP)诱导的血小板聚集抑制率和氯吡格雷抵抗的影响。方法:选取皖南医学院弋矶山医院2016年6月至2017年7月接受阿司匹林和氯吡格雷双抗治疗患者163例为研究对象,采用荧光染色原位杂交检测患者CYP2C19*2、*3和*17基因型,依据基因型将CYP2C19酶活性分为快代谢型(RM)、中间代谢型(IM)、慢代谢型(PM)和超快代谢型(UM)。患者给药5 d后,采用血栓弹力图仪检测患者ADP诱导的血小板聚集抑制率(IPAADP),评价CYP2C19*2、*3和*17基因型和CYP2C19酶不同代谢型IPAADP差异性,CYP2C19基因型和代谢型以及在氯吡格雷抵抗组(CR)和非氯吡格雷抵抗组(NCR)分布。结果:CYP2C19*2、*3和*17突变率分别为30.98%、6.75%和1.23%。IPAADP平均为(67.03±26.79)%,其中CR发生率26.99%,其IPAADP为(31.29±12.60)%。CYP2C19*2和*3基因携带者IPAADP明显降低(P<0.001),*17基因携带者IPAADP明显升高(P<0.001)。24例(14.72%)为PM型,各代谢型IPAADP比较差异无统计学意义(P>0.05)。CYP2C19基因型和代谢型在NCR和CR中分布无统计学差异(P>0.05)。结论:CYP2C19基因型对IPAADP有显著影响,但与CR的发生无关联性,相关研究还需进一步验证。AIM:To investigate the effect of the polymorphism and metabolic type of cytochrome P450(CYP)2 C19 gene on the inhibitory rate of platelet aggregation induced by ADP and relationship with resistance of clopidogrel.METHODS:A total of 163 patients that are administrated with aspirin and clopidogrel were collected from the Yijishan Hospital of Wannan Medical College from June 2016 to July 2017.The CYP2 C19*2,*3 and*17 genotypes of patients were detected with fluorescence staining in situ hybridization,according to the genotype,CYP2 C19 enzyme activity was divided into fast metabolic(RM),intermediate metabolic(IM),slow metabolic(PM)and ultrafast metabolic type(UM).After 5 days of drug delivery,the platelet aggregation inhibition rate(IPAADP)induced by ADP was detected by thrombus elasto graph.IPAADP differences between CYP2 C19*2,*3 and*17 genotype and CYP2 C19 enzyme metabolic type were evaluated.CYP2 C19 genotype and metabolic type as well as their distribution in clopidogrel resistance group(CR)and non clopidogrel resistance group(NCR)were observed.RESULTS:The mutation rates of CYP2 C19*2,*3 and*17 were 30.98%,6.75%and 1.23%,respectively.The average IPAADPwas(67.03±26.79)%and the incidence of CR was 26.99%,and the IPAADPwas(31.29±12.60)%.The IPAADPof CYP2 C19*2 and*3 gene carriers were decreased significantly(P<0.001),and the IPAADPof*17 gene carriers were increased significantly(P<0.001).Twenty-four cases(14.72%)were type PM,and there was no statistical difference in IPAADPbetween each metabolic type(P>0.05).There was no statistical difference in the distribution of CYP2 C19 genotypes and metabolic types in NCR and CR(P>0.05).CONCLUSION:CYP2 C19 genotypes have significant effect on IPAADP,but there is no association with the occurrence of CR,and the related study needs to be further verified.

关 键 词：CYP2C19基因多态性 氯吡格雷抵抗 血小板聚集抑制率 精准用药 药效学评价 

分 类 号：R541.1[医药卫生—心血管疾病] R969.1[医药卫生—内科学]