title: Cytochrome allelic variants and clopidogrel metabolism in cardiovascular diseases therapy.
abstract: Clopidogrel and aspirin are among the most prescribed dual antiplatelet therapies to treat the acute coronary syndrome and heart attacks. However, their potential clinical impacts are a subject of intense debates. The therapeutic efficiency of clopidogrel is controlled by the actions of hepatic cytochrome P450 (CYPs) enzymes and impacted by individual genetic variations. Inter-individual polymorphisms in CYPs enzymes affect the metabolism of clopidogrel into its active metabolites and, therefore, modify its turnover and clinical outcome. So far, clinical trials fail to confirm higher or lower adverse cardiovascular effects in patients treated with combinations of clopidogrel and proton pump inhibitors, compared with clopidogrel alone. Such inconclusive findings may be due to genetic variations in the cytochromes CYP2C19 and CYP3A4/5. To investigate potential interactions/effects of these cytochromes and their allele variants on the treatment of acute coronary syndrome with clopidogrel alone or in combination with proton pump inhibitors, we analyze recent literature and discuss the potential impact of the cytochrome allelic variants on cardiovascular events and stent thrombosis treated with clopidogrel. The diversity of CYP2C19 polymorphisms and prevalence span within various ethnic groups, subpopulations and demographic areas are also debated.
authors.affiliation: College of Biotechnology, University of Modern Sciences, Dubai, United Arab Emirates.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jarrar
authors.affiliation: College of Biotechnology, University of Modern Sciences, Dubai, United Arab Emirates.
authors.forename: Shalini
authors.initials: S
authors.lastname: Behl
authors.affiliation: Department of Bioinformatics & Computational Biology, The UT MD Anderson Cancer Center, Houston, TX, 77054, USA.
authors.forename: Ganiraju
authors.initials: G
authors.lastname: Manyam
authors.affiliation: College of Biotechnology, University of Modern Sciences, Dubai, United Arab Emirates.
authors.forename: Hany
authors.initials: H
authors.lastname: Ganah
authors.affiliation: College of Biotechnology, University of Modern Sciences, Dubai, United Arab Emirates.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Nazir
authors.affiliation: College of Biotechnology, University of Modern Sciences, Dubai, United Arab Emirates.
authors.forename: Reem
authors.initials: R
authors.lastname: Nasab
authors.affiliation: Conservatoire National des Arts et Métiers, Paris, France. khaled.moustafa@gmail.com.
authors.forename: Khaled
authors.initials: K
authors.lastname: Moustafa
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000077144:Clopidogrel; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004359:Drug Therapy, Combination; D005787:Gene Frequency; D006801:Humans; D008658:Inactivation, Metabolic; D000071184:Pharmacogenomic Variants; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Acute coronary syndrome; Biodrugs; CYP2C19; CYP3A4; Cardiovascular events; Clopidogrel; Clopidogrel metabolism; Proton pump inhibitors