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Clopidogrel utilization in patients with coronary artery disease and diabetes mellitus: should we determine CYP2C19*2 genotype?

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Clopidogrel non-responsiveness is multifactorial; several genetic and non-genetic factors may contribute to impaired platelet inhibition. The goal of this study is to determine the effect of the cytochrome P450 CYP2C19*2 polymorphism on the platelet response to clopidogrel in patients with and without diabetes mellitus (DM).

Methods

We conducted an observational study in patients with coronary artery disease and consequent exposure to clopidogrel therapy (75 mg/day for at least 7 consecutive days). We have analyzed two groups of patients: group I (DM patients) and group II (non-diabetes mellitus patients). Platelet reactivity was assessed by the VerifyNow P2Y12 assay and high on clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) ≥ 208. Genotyping for CYP2C19*2 polymorphism was performed by PCR-RFLP.

Results

We have included 150 subjects (76 DM and 74 non-diabetes mellitus patients). The carriage of CYP2C19*2 allele, in DM patients, was significantly associated to HPR (odds ratio (OR) 4.437, 95% confidence interval (CI) 1.134 to 17.359; p = 0.032). Furthermore, 8.4% of the variability in percent inhibition by clopidogrel could be attributed to CYP2C19*2 carrier status. However, in non-diabetes mellitus patients, there was no significant difference in platelet response to clopidogrel according to the presence or absence of CYP2C19*2 allele carriage (OR 1.260, 95% CI 0.288 to 5.522; p = 0.759).

Conclusions

Our study suggests that the carriage of CYP2C19*2 polymorphism, in DM patients, might be a potential predictor of persisting HPR in these high-risk individuals.

Trial registration

Clinical Trials.gov NCT03373552 (Registered 13 December 2017)

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Acknowledgements

The authors are very grateful to all patients who participated in this study.

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Authors and Affiliations

  1. Hematology Department, Fattouma Bourguiba University Hospital, TN 5000, Monastir, Tunisia

    Saoussen Chouchene, Fatma Abderrazak, Mayssa Gaaloul, Marwa Rezek & Mohsen Hassine

  2. Biochemistry and Molecular Biology Laboratory (LR00SP03), Children’s Hospital Bechir Hamza, 1006, Tunis, Tunisia

    Rym Dabboubi, Sondess Hadj Fredj & Taieb Messaoud

  3. Cardiology Department, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia

    Haythem Raddaoui, Khaldoun Ben Hamda & Faouzi Maatouk

  4. Epidemiology and Preventive Medicine Department, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia

    Hela Abroug & Asma Sriha

  5. Biochemistry Department, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia

    Fadoua Neffeti, Ilhem Hellara & Mohamed Fadhel Najjar

  6. Biology Department, Maternity and Neonatal Medicine Center, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia

    Mouna Sassi & Linda Khefacha

  7. Research Laboratory (LR12SP18), University of Monastir, 5000, Monastir, Tunisia

    Semir Nouira

Authors
  1. Saoussen Chouchene
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  2. Rym Dabboubi
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  3. Haythem Raddaoui
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  4. Hela Abroug
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  5. Khaldoun Ben Hamda
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  6. Sondess Hadj Fredj
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  10. Fadoua Neffeti
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  17. Faouzi Maatouk
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  18. Taieb Messaoud
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  19. Mohsen Hassine
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Contributions

SC designed the study, performed data analysis, and wrote the manuscript. HR, MG, and MR included the patients. RD and SHF performed genetic analysis and reviewed the manuscript. HA and AS conducted the statistical analysis. FA, FN, IH, MS, and LK supervised results. SN, KBH, FM, MFN, TM, and MH revised critically the intellectual content of the manuscript.

Corresponding author

Correspondence to Saoussen Chouchene.

Ethics declarations

The study protocol was approved by the Ethics Committee for Clinical Research at our center and all subjects gave informed consent for study participation.

Conflict of interest

The authors declare that they have no competing interests.

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Chouchene, S., Dabboubi, R., Raddaoui, H. et al. Clopidogrel utilization in patients with coronary artery disease and diabetes mellitus: should we determine CYP2C19*2 genotype?. Eur J Clin Pharmacol 74, 1567–1574 (2018). https://doi.org/10.1007/s00228-018-2530-5

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