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Effect of cytochrome P450 2C19 polymorphism on adverse cardiovascular events after drug-eluting stent implantation in a large Hakka population with acute coronary syndrome receiving clopidogrel in southern China

  • Pharmacogenetics
  • Published:
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Abstract

Background and objectives

The objective of this study is to evaluate the effects of cytochrome P450 2C19 (CYP2C19) polymorphism on adverse cardiovascular events (MACE) in Hakka patients with acute coronary syndrome (ACS) receiving clopidogrel who had undergone coronary drug-eluting stent placement after percutaneous coronary intervention (PCI) in southern China.

Methods

Genotyping of CYP2C19 and MACE of 934 ACS patients with PCI on clopidogrel maintenance therapy were analyzed. Patients who carried loss-of-function CYP2C19 were treated with a 150-mg maintenance dose of clopidogrel or 90 mg of ticagrelor antiplatelet therapy, and patients who were non-carriers received clopidogrel therapy daily at a maintenance dose of 75 mg and the patients were followed-up for at least 12 months. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, and target vessel revascularization and stroke.

Results

The allelic frequency of CYP2C19*2 and CYP2C19*3 of Hakka patients in the current study was 31.64 and 5.19%, respectively. The CYP2C19 wild-type homozygotes (*1/*1) were the most predominant among the patients (40.36%), followed by the CYP2C19*2 heterozygotes (*1/*2) (40.26%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM; 40.36%), intermediate metabolizers (IM; 45.61%), and poor metabolizers (PM; 14.03%). Based on the genotype-guided antiplatelet therapy, there was no significant association between the carrier status and the clinical outcome at 1, 6, and 12 months. In addition, no significant difference in the rates of bleeding was found among the three groups. After logistic regression analysis, hypertension was the only independent predictor of cardiovascular events (relative risk, 1.501; 95% CI, 1.011 to 2.229; P = 0.044).

Conclusions

Our results shed new light on the important benefit of testing CYP2C19 polymorphisms before prescribing clopidogrel in patients treated with drug-eluting stent implantation after PCI. The testing may help to optimize pharmacotherapy effectiveness by providing individualized treatment to the Chinese population. Our findings mandate further studies aimed at initiating genome-based personalized antiplatelet therapy in a Hakka population in southern China.

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Funding

This study was supported by The National Key Research and Development Program of China (Grant No.: 2016YFD0050405 to Dr. Pingsen Zhao), Natural Science Foundation of Guangdong Province, China (Grant No.: 2014A030307042 to Dr. Pingsen Zhao), Medical Scientific Research Foundation of Guangdong Province, China (Grant No.: A2016306 to Dr. Pingsen Zhao), Natural Science Foundation of Guangdong Province, China (Grant No.: 2016A030307031 to Dr. Pingsen Zhao), The National Key Research and Development Program of China (Grant No.: 2017YFD0501705 to Dr. Pingsen Zhao), Medical Scientific Research Foundation of Guangdong Province, China (Grant No.: A2017404 to Dr. Jingyuan Hou), Key Scientific and Technological Project of Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Guangdong Province, China (Grant No.: MPHKSTP-20170102 to Pingsen Zhao), and Key Scientific and Technological Project of Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Guangdong Province, China (Grant No.: MPHKSTP-20170101 to Zhixiong Zhong).

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Author notes

  1. Zhixiong Zhong and Jingyuan Hou contributed equally to this work.

Authors and Affiliations

  1. Center for Cardiovascular Diseases, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, 514031, People’s Republic of China

    Zhixiong Zhong, Qifeng Zhang, Bin Li, Cunren Li, Zhidong Liu, Min Yang, Wei Zhong & Xuebo He

  2. Clinical Core Laboratory, Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, 514031, People’s Republic of China

    Jingyuan Hou, Hesen Wu, Miaocai Zhong & Pingsen Zhao

  3. Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, 514031, People’s Republic of China

    Hesen Wu, Miaocai Zhong & Pingsen Zhao

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  1. Zhixiong Zhong
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  4. Bin Li
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  12. Pingsen Zhao
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Contributions

Pingsen Zhao conceived and designed the experiments; Zhixiong Zhong, Qifeng Zhang, Bin Li, Cunren Li, Zhidong Liu, Min Yang, Wei Zhong, and Xuebo He collected the clinical data and samples; Jingyuan Hou, Hesen Wu, and Miaocai Zhong performed the experiments; Pingsen Zhao, Zhixiong Zhong, and Jingyuan Hou analyzed the data and wrote the paper. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Pingsen Zhao.

Ethics declarations

The study protocol was in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Ethics Committee of Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University. Written informed consent was obtained from all enrolled patients, and their privacy was strictly protected.

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The authors declare that they have no conflict of interest.

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Zhong, Z., Hou, J., Zhang, Q. et al. Effect of cytochrome P450 2C19 polymorphism on adverse cardiovascular events after drug-eluting stent implantation in a large Hakka population with acute coronary syndrome receiving clopidogrel in southern China. Eur J Clin Pharmacol 74, 423–431 (2018). https://doi.org/10.1007/s00228-017-2393-1

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