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Genetic determinants of on-clopidogrel high platelet reactivity

Campo, Gianluca ; Miccoli, Matteo ; Tebaldi, Matteo ; Marchesini, Jlenia ; Fileti, Luca ; Monti, Monia ; Valgimigli, Marco ; Ferrari, Roberto

Platelets (Edinburgh), 2011-09, Vol.22 (6), p.399-407 [Periódico revisado por pares]

England: Informa UK, Ltd

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Título:
Genetic determinants of on-clopidogrel high platelet reactivity
Autor: Campo, Gianluca ; Miccoli, Matteo ; Tebaldi, Matteo ; Marchesini, Jlenia ; Fileti, Luca ; Monti, Monia ; Valgimigli, Marco ; Ferrari, Roberto
Assuntos: Aryl Hydrocarbon Hydroxylases - genetics ; Aryl Hydrocarbon Hydroxylases - metabolism ; Aryldialkylphosphatase - genetics ; Aryldialkylphosphatase - metabolism ; Aspirin - pharmacology ; ATP Binding Cassette Transporter, Sub-Family B - genetics ; ATP Binding Cassette Transporter, Sub-Family B - metabolism ; Biomarkers, Pharmacological - analysis ; Blood Platelets - cytology ; Blood Platelets - metabolism ; Clopidogrel, gene polymorphism, clinical outcome, platelet reactivity ; Drug Combinations ; Genetic Testing ; Humans ; Liver - enzymology ; Liver - pathology ; Mutation ; Platelet Aggregation - drug effects ; Platelet Aggregation Inhibitors - pharmacology ; Platelet Aggregation Inhibitors - therapeutic use ; Polymorphism, Genetic ; Prodrugs - metabolism ; Prodrugs - pharmacology ; Risk Factors ; Thrombosis - drug therapy ; Thrombosis - genetics ; Thrombosis - metabolism ; Thrombosis - pathology ; Thrombosis - prevention & control ; Ticlopidine - analogs & derivatives ; Ticlopidine - metabolism ; Ticlopidine - pharmacology ; Treatment Outcome
É parte de: Platelets (Edinburgh), 2011-09, Vol.22 (6), p.399-407
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
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ObjectType-Review-1
Descrição: Clopidogrel has been used (alone or in association with aspirin) to prevent vascular complications in atherothrombotic patients, to prevent stent thrombosis (ST) in patients undergoing percutaneous coronary intervention (PCI) and as a long-term prevention of cardiovascular and cerebrovascular events. Unfortunately, it is important to note that there are a number of patients who, during clopidogrel therapy, show and maintain a high platelet reactivity (PR), similar to that observed before the start of antiplatelet therapy. Clopidogrel pro-drug is absorbed in the intestine and this process is influenced by P-glycoprotein-1 (P-GP). Its conversion into 2-oxo clopidogrel is regulated by cytochromes (CYP) called CYP2C19, CYP2B6 and CYP1A2. Whereas, the final transformation into the active metabolite is regulated by CYP called CYP2C19, CYP2C9, CYP2B6, CYP3A4, CYP3A5 and, as recently emerged, by the glycoprotein paraoxonase-1 (PON1). The genes encoding these enzymes are characterized by several polymorphisms. Some of these are able to modify the activity of proteins, reducing the concentration of active metabolite and the values of on-clopidogrel PR. Only one gene polymorphism (CYP2C19*17) increases the clopidogrel metabolization and so the clopidogrel-induced platelet inhibition. Several studies have clearly associated these gene polymorphisms to both ischemic and bleeding complications in patients receiving dual antiplatelet therapy. The aim of this review is to describe the principal gene polymorphisms influencing on-clopidogrel PR and their relationship with long-term clinical outcome.
Editor: England: Informa UK, Ltd
Idioma: Inglês

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Genetic determinants of on-clopidogrel high platelet reactivity

Campo, Gianluca ; Miccoli, Matteo ; Tebaldi, Matteo ; Marchesini, Jlenia ; Fileti, Luca ; Monti, Monia ; Valgimigli, Marco ; Ferrari, Roberto

England: Informa UK, Ltd

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