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

doi:10.12092/j.issn.1009-2501.2020.07.005

中国临床药理学与治疗学 ›› 2020, Vol. 25 ›› Issue (7): 746-751.doi: 10.12092/j.issn.1009-2501.2020.07.005

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

彭静，刘俊，许慧芳，李越然，江佳，汪盛，周德喜，朱艳虹，杨魁，栾家杰

皖南医学院弋矶山医院药学部，芜湖 241001，安徽

收稿日期:2020-02-21 修回日期:2020-06-09 出版日期:2020-07-26 发布日期:2020-07-31
通讯作者: 刘俊，通信作者，本科，副主任药师，研究方向：临床药学。 E-mail: xiaoyu234561@sina.com
作者简介:彭静，女，本科，主管药师，研究方向：临床药学。 Tel: 13955300199 E-mail: 3307919936@qq.com
基金资助:
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）

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

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

Received:2020-02-21 Revised:2020-06-09 Online:2020-07-26 Published:2020-07-31

摘要/Abstract

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。

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

Abstract: AIM: To investigate the effect of the polymorphism and metabolic type of cytochrome P450 (CYP) 2C19 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 CYP2C19*2, *3 and *17 genotypes of patients were detected with fluorescence staining in situ hybridization, according to the genotype, CYP2C19 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 CYP2C19*2, *3 and *17 genotype and CYP2C19 enzyme metabolic type were evaluated. CYP2C19 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 CYP2C19*2, *3 and *17 were 30.98%, 6.75% and 1.23%, respectively. The average IPAADP was (67.03±26.79)% and the incidence of CR was 26.99%, and the IPAADP was (31.29±12.60)%. The IPAADP of CYP2C19*2 and *3 gene carriers were decreased significantly (P<0.001), and the IPAADP of *17 gene carriers were increased significantly (P<0.001). Twenty-four cases (14.72%) were type PM, and there was no statistical difference in IPAADP between each metabolic type (P>0.05). There was no statistical difference in the distribution of CYP2C19 genotypes and metabolic types in NCR and CR (P>0.05). CONCLUSION: CYP2C19 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.

Key words: CYP2C19 gene polymorphism, clopidogrel resistance, platelet aggregation inhibition rate, precise medication, pharmacodynamic evaluation

中图分类号:

彭静, 刘俊, 许慧芳, 李越然, 江佳, 汪盛, 周德喜, 朱艳虹, 杨魁, 栾家杰. 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[J]. 中国临床药理学与治疗学, 2020, 25(7): 746-751.

PENG Jing, LIU Jun, XU Huifang, LI Yueran, JIANG Jia, WANG Sheng, ZHOU Dexi, ZHU Yanhong, YANG Kui, LUAN Jiajie. Correlation study between cytochrome P4502C19 gene polymorphism or metabolic type and ADP induced-platelet aggregation inhibition and clopidogrel resistance[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(7): 746-751.

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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

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