title: Genetic determinants of platelet response to clopidogrel.
abstract: Antiplatelet agents are the mainstay treatment in the prevention and management of atherothrombotic complications. However, a substantial interpatient variability in response to clopidogrel has been reported. Furthermore, patients with coronary artery disease and lesser platelet inhibition in response to clopidogrel are at increased risk for cardiovascular events. Clopidogrel after absorption requires two-step oxidation by the hepatic cytochrome P450 to generate its active metabolite. Polymorphisms of genes encoding the cytochrome enzymes and P-glycoprotein involved in clopidogrel absorption are regarded as major determinants of the interindividual variability in the clopidogrel-induced platelet inhibition. In our review we discuss the prevalence and clinical significance of various alleles of the genes: CYP2C19 and ABCB1 in the setting of coronary artery disease. Allele CYP2C19*2 is associated with excess of ischaemic events including myocardial infarction and stent thrombosis. On the other hand, CYP2C19*17 allele poses a serious threat of bleeding. Data concerning the prognostic value of genetic variant 3435C→T of ABCB1 remain inconclusive.
authors.affiliation: Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, 3 Technikow Street, 85-801 Bydgoszcz, Poland.
authors.forename: Aldona
authors.initials: A
authors.lastname: Kubica
authors.forename: Marek
authors.initials: M
authors.lastname: Kozinski
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Grzesk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Fabiszak
authors.forename: Eliano Pio
authors.initials: EP
authors.lastname: Navarese
authors.forename: Aleksander
authors.initials: A
authors.lastname: Goch
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D010975:Platelet Aggregation Inhibitors; D011110:Polymorphism, Genetic; D011379:Prognosis; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine