Clopidogrel pharmacogenetics and its clinical implications. Am J Ther 2010;17(3):e66-73
Date
07/29/2009Pubmed ID
19636246DOI
10.1097/MJT.0b013e3181afbf62Scopus ID
2-s2.0-77952512291 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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.
Author List
Singh M, Thapa B, Arora RAuthor
Bipin Thapa MD Assistant Dean, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Blood PlateletsCytochrome P-450 Enzyme System
Humans
Integrin alpha2beta1
Pharmacogenetics
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex
Polymorphism, Genetic
Receptors, Purinergic P2
Receptors, Purinergic P2Y12
Ticlopidine