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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2020, Vol. 25 ›› Issue (7): 746-751.doi: 10.12092/j.issn.1009-2501.2020.07.005

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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   

  1. 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

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

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