Genetic determinants of platelet response to clopidogrel |
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Authors: | Aldona Kubica Marek Kozinski Grzegorz Grzesk Tomasz Fabiszak Eliano Pio Navarese Aleksander Goch |
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Institution: | (1) Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, 3 Technikow Street, 85-801 Bydgoszcz, Poland;(2) Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland;(3) Department of Pharmacology and Therapy, Collegium Medicum, Nicolaus Copernicus University, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland; |
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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. |
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