Saoussen Chouchene1, Rym Dabboubi2, Haythem Raddaoui3, Hela Abroug4, Khaldoun Ben Hamda3, Sondess Hadj Fredj2, Fatma Abderrazak5, Mayssa Gaaloul5, Marwa Rezek5, Fadoua Neffeti6, Ilhem Hellara6, Mouna Sassi7, Linda Khefacha7, Asma Sriha4, Semir Nouira8, Mohamed Fadhel Najjar6, Faouzi Maatouk3, Taieb Messaoud2, Mohsen Hassine5. 1. Hematology Department, Fattouma Bourguiba University Hospital, TN 5000, Monastir, Tunisia. saoussen_chouchene@yahoo.fr. 2. Biochemistry and Molecular Biology Laboratory (LR00SP03), Children's Hospital Bechir Hamza, 1006, Tunis, Tunisia. 3. Cardiology Department, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia. 4. Epidemiology and Preventive Medicine Department, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia. 5. Hematology Department, Fattouma Bourguiba University Hospital, TN 5000, Monastir, Tunisia. 6. Biochemistry Department, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia. 7. Biology Department, Maternity and Neonatal Medicine Center, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia. 8. Research Laboratory (LR12SP18), University of Monastir, 5000, Monastir, Tunisia.
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).
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 (DMpatients) and group II (non-diabetes mellituspatients). 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 mellituspatients). The carriage of CYP2C19*2 allele, in DMpatients, 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 mellituspatients, 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 DMpatients, 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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