Clopidogrel pharmacogenetics and its clinical implications.
Pharmacogenetics encompasses a range of phenomena ranging from pharmacology to therapeutics to toxicology and generally focuses on the study of genetic factors related to interindividual variability in drug response. Individual differences in the rate of platelet reactivity markedly influence normal hemostasis and the pathologic outcome of thrombosis. Response to clopidogrel varies widely, with nonresponse rates in various studies ranging from 4%-30% at 24 hours. Polymorphism involved in the response to antithrombotic drugs has been described in components of the hemostatic and thrombotic systems, and these include genetic variations. Polymorphisms in the hepatic enzymes involved in the metabolism of clopidogrel (e.g., CYP 1A2, CYP3A4, CYP2C19) or within the platelet membrane receptor (P2Y12) and/or polymorphism of platelet integrin alphaIIbbeta3 or integrin alpha2beta1 may affect platelet responses and could influence response to clopidogrel administration. In this review, we discuss the pharmacogenetics of clopidogrel related to the phenomenon of response variability and its clinical implications.
Singh
Mukesh
M
Section of Cardiology, Department of Internal Medicine, Rosalind Franklin University of Medicine & Science, Chicago Medical School, North Chicago, IL, USA. drmukeshsingh@yahoo.com
Thapa
Bipin
B
Arora
Rohit
R
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000077144:Clopidogrel; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D018048:Receptors, Purinergic P2 / Q000235:genetics; D058925:Receptors, Purinergic P2Y12; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D038982:Integrin alpha2beta1; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D013988:Ticlopidine