Influence of CYP450 Enzymes and ABCB1 Polymorphisms on Clopidogrel Response in Moroccan Patients with Acute Coronary Syndromes

Ismail Mouhrach,1,2 Laila Bouguenouch,2,3 Adil Kamal,3,4 Abbassi Meriame,2 Nada El Khorb,3,4 Mohammed El Azami El Idrissi,3 Hafid Akoudad,3,4 Hicham Bekkari1 1Laboratory of Biotechnology, Environment, Agrifood, and Health, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco; 2Department of Medical Genetics and Oncogenetics, University Hospital Hassan II, Fez, Morocco; 3Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, Morocco; 4Department of Cardiology, University Hospital Hassan II, Fez, MoroccoCorrespondence: Ismail Mouhrach, Laboratory of Biotechnology, Environment, Agrifood, and Health, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, B.P. 1796 Fès-Atlas, Fez, 30003, Morocco, Tel +212 7 08 02 96 10, Fax +212535642500, Email ismail.mouhrach@usmba.ac.maIntroduction: Clopidogrel is an antiplatelet prodrug primarily prescribed to prevent or treat acute coronary syndrome (ACS) or acute ischemic stroke (IS), polymorphisms of genes encoding cytochrome P-450 (CYP) and P-glycoprotein transporter, could affect the efficiency of clopidogrel absorption and biotransformation, especially during the first critical hours following its administration.Methods: The present study was designed to investigate the potential association of clopidogrel responsiveness and 14 polymorphisms in the genes encoding the CYPs (CYP2C9, 2C19, 3A4, 3A5, 1A2, and 2B6), the ATP binding cassette subfamily B member 1 (ABCB1). Platelet aggregation activity was measured after 8h of 300mg clopidogrel administration for fifty-five ACS patients.Results: There was no significant association between polymorphism of the studied CYPs and clopidogrel responsiveness (P> 0.05). The frequency of the ABCB1 3435 T allele in clopidogrel non-responders was higher (78.9%) compared to responders (52.8%), but this difference was not significant (P=0.057). Demographic characteristics, comorbidities, concomitant treatments were not associated with clopidogrel response.Discussion: There was no effect of the studied genetic variations and demographic factors on the platelet activity of clopidogrel in Moroccan ACS patients.Keywords: clopidogrel resistance, coronary artery disease, gene polymorphisms, platelet inhibitors, ABCB1 gene, CYP450 gene