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The genetics of antiplatelet drug resistance
Author(s) -
Feher G,
Feher A,
Pusch G,
Lupkovics G,
Szapary L,
Papp E
Publication year - 2009
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2008.01105.x
Subject(s) - clopidogrel , medicine , platelet , hemostasis , aspirin , antiplatelet drug , thrombosis , platelet activation , cyclooxygenase , p2y12 , pharmacology , cardiology , biology , enzyme , biochemistry
Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets’ response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)‐1, COX‐2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y 1 , P2Y 12 , CYP2C9, CYP3A4 and CYP3A5 genotypes.