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CYP2C19*2 genetic polymorphism and incidence of in-stent restenosis in patients on clopidogrel: a matched case-control study

  • Sara Osama , Francesca Wirth ORCID logo EMAIL logo , Graziella Zahra , Christopher Barbara , Robert G. Xuereb , Liberato Camilleri and Lilian M. Azzopardi
Published/Copyright: January 1, 2021
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Drug Metabolism and Personalized Therapy
From the journal Drug Metabolism and Personalized Therapy Volume 37 Issue 2

Abstract

Objectives

The cytochrome P450 2C19*2 (CYP2C19*2) genetic polymorphism is associated with reduced clopidogrel bioactivation, increasing the risk of atherothrombotic complications after percutaneous coronary intervention (PCI). In-stent restenosis (ISR) is a complication that limits the long-term prognosis of PCI. The aim was to investigate the association between presence of the CYP2C19*2 allele and ISR within one-year after PCI in patients prescribed dual antiplatelet therapy with aspirin and clopidogrel.

Methods

Sixty patients with angiographically-confirmed drug eluting stent (DES)-ISR within 12 months post-PCI when on DAPT with aspirin and clopidogrel were retrospectively identified (Cases). Another 60 patients with no documented ISR post-PCI in the study period (Controls) were case-matched for age, gender, ethnicity, diabetes mellitus and estimated glomerular filtration rate value, and were invited for CYP2C19*2 genotyping. The association between presence of the CYP2C19*2 allele and ISR was analysed using the Fisher’s exact test and binary logistic regression.

Results

Twenty-six (43.3%) cases and 5 (8.3%) controls were carriers of one or two CYP2C19*2 alleles. As to non-carrier status of the CYP2C19*2 allele, 34 (56.7%) cases and 55 (91.7%) controls were identified. The association between CYP2C19*2 carrier status and DES-ISR within one-year post-PCI was statistically significant (p<0.001) in both the univariate and multivariate analysis.

Conclusions

The proportion of patients who were carriers of one or two CYP2C19*2 alleles who presented with DES-ISR within one-year post-PCI while on clopidogrel was significantly higher compared to patients with no documented ISR.

Keywords: clopidogrel; CYP2C19*2 genetic polymorphism; in-stent restenosis; percutaneous coronary intervention; pharmacogenetics; precision antiplatelet therapy
Corresponding author: Francesca Wirth, Department of Pharmacy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta, E-mail:

Funding source: University of Malta Research Grant N/A

Award Identifier / Grant number: PHRRP12-19

Acknowledgments

The authors acknowledge all the consultant cardiologists and staff at the Department of Cardiology, staff at the Molecular Diagnostics Unit and Phlebotomy Clinic of Mater Dei Hospital, for their support during patient recruitment and genotyping.

  1. Research funding: The research was financially supported by University of Malta Research Grant PHRRP12-19.

  2. Author contributions: Sara Osama performed the study and drafted the manuscript. Francesca Wirth developed the study design, supervised the study and reviewed the manuscript. Graziella Zahra and Christopher Barbara oversaw the laboratory work and reviewed the manuscript. Robert G Xuereb and Lilian M Azzopardi brought clinical expertise to interpret results and reviewed the manuscript. Liberato Camilleri supported the statistical analysis and reviewed the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The authors declare that there is no conflict of interest to disclose.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study was approved by the University of Malta Faculty of Medicine and Surgery Research Ethics Committee (Ref. No. FRECMDS_1819_59).

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Received: 2021-07-12
Accepted: 2021-10-01
Published Online: 2021-01-01

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/dmpt-2021-0160
Keywords for this article
clopidogrel; CYP2C19*2 genetic polymorphism; in-stent restenosis; percutaneous coronary intervention; pharmacogenetics; precision antiplatelet therapy

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Potentials of autophagy enhancing natural products in the treatment of Parkinson disease
  4. Genetic polymorphisms of reproductive hormones and their receptors in assisted reproduction technology for patients with polycystic ovary syndrome
  5. Minireview
  6. Influence of GSTM1, GSTT1, and GSTP1 genetic polymorphisms on disorders in transplant patients: a systematic review
  7. Original Articles
  8. Modifying effects of TNF-α, IL-6 and VDR genes on the development risk and the course of COVID-19. Pilot study
  9. Prevalence of ABCB1 3435C>T polymorphism in the Cuban population
  10. The association of cytochrome 7A1 and ATP-binding cassette G8 genotypes with type 2 diabetes among Jordanian patients
  11. CYP2C19*2 genetic polymorphism and incidence of in-stent restenosis in patients on clopidogrel: a matched case-control study
  12. Study of the pharmacokinetics of various drugs under conditions of antiorthostatic hypokinesia and the pharmacokinetics of acetaminophen under long-term spaceflight conditions
  13. Virgin coconut oil abrogates depression-associated cognitive deficits by modulating hippocampal antioxidant balance, GABAergic and glutamatergic receptors in mice
  14. Cnestis ferruginea Vahl ex DC (Connaraceae) downregulates expression of immediate early genes in kainic acid-induced temporal lobe epilepsy in mice
  15. Toxicological evaluation of hydroethanol leaf extract of Pupalia lappacea (Linn.) Juss. (Amaranthaceae) in rodents
  16. Short Communication
  17. Comparison of different autoanalyzers for the determination of lymphocyte and neutrophil counts in mouse blood
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