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Clopidogrel Pharmacogenetics in Iranian Patients Undergoing Percutaneous Coronary Intervention

  • Nejat Mahdieh
  • Ahmad Rabbani
  • Ata Firouzi
  • Ali Zahedmehr
  • Maryam Hoseinimoghaddam
  • Sedigheh Saedi
  • Hamidreza Sanati
  • Hosseinali Basiri
  • Feridoun Noohi
  • Bahareh Rabbani
  • Majid Maleki
Article
  • 63 Downloads

Abstract

Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow-up; common variants of CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes were determined as well as the patients’ cardiovascular outcomes to find out the effect of these variants individually and in combination. 388 individuals receiving PCI were enrolled in this study. Different pretreatment doses of clopidogrel were prescribed under the interventional cardiologists’ guidance. The patients were followed for a duration of 1 month, and 6 months. Six SNPs were selected for genotyping including CYP2C19*2 (c.681G > A), CYP2C19*3 (c.636G > A), CYP2C19*17 allele (c.−806C > T), ABCB1 (c.3435C > T), CYP3A5 (c.6986A > G), and CYP3A4 (c.1026 + 12G > A). The mean loading dose was 600 mg/day in 267 (68.8%) individuals, 300 mg/day in 121 (31.2%). 8 patients had cardiovascular events such as thrombosis, unstable angina, and non-STEMI. The studied alleles and genotypes were in Hardy–Weinberg equilibrium. None of the SNPs individually were significantly associated with outcome events. Our results indicate that combinations of different alleles of genes are involved in pharmacokinetic variability and joint factors are important; this means that genotyping and analysis of an individual variant may not be as straightforward in risk assessment and pharmacogenetics. This highlights the importance of personalized medicine in risk assessment and treatment.

Keywords

Genetic variants Polymorphism Clopidogrel Cardiovascular event 

Notes

Acknowledgements

We would like to thank the staff of genetic laboratory at Rajaie Hospital. We would like to thank professor Edward Tuddenham for critical reading of the manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflict of interest to declare in relation to this manuscript.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018
Corrected publication August/2018

Authors and Affiliations

  • Nejat Mahdieh
    • 1
  • Ahmad Rabbani
    • 2
  • Ata Firouzi
    • 2
  • Ali Zahedmehr
    • 2
  • Maryam Hoseinimoghaddam
    • 1
  • Sedigheh Saedi
    • 2
  • Hamidreza Sanati
    • 2
  • Hosseinali Basiri
    • 2
  • Feridoun Noohi
    • 2
  • Bahareh Rabbani
    • 1
    • 3
  • Majid Maleki
    • 1
  1. 1.Medical Genetics Laboratory, Rajaie Cardiovascular Medical and Research CenterIran University of Medical SciencesTehranIran
  2. 2.Rajaie Cardiovascular Medical and Research CenterIran University of Medical SciencesTehranIran
  3. 3.Growth and Development ResearchTehran University of Medical SciencesTehranIran

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