STATE-OF-THE-ART PAPER
Pharmacogenetics in Cardiovascular Antithrombotic Therapy
Francisco Marín, MD, PhD*,
Rocío González-Conejero, PhD ,
Piera Capranzano, MD ,
Theodore A. Bass, MD,
Vanessa Roldán, MD, PhD and
Dominick J. Angiolillo, MD, PhD,*
* Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
Centro de Hemodonación, Universidad de Murcia, Murcia, Spain
Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida
Manuscript received December 23, 2008;
revised manuscript received March 25, 2009,
accepted April 14, 2009.
* Reprint requests and correspondence: Dr. Dominick J. Angiolillo, Division of Cardiology, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, Florida 32209 (Email: Dominick.angiolillo{at}jax.ufl.edu).
Thrombosis is the most important underlying mechanism of coronary artery disease and embolic stroke. Hence, antithrombotic therapy is widely used in these scenarios. However, not all patients achieve the same degree of benefit from antithrombotic agents, and a considerable number of treated patients will continue to experience a new thrombotic event. Such lack of clinical benefit may be related to a wide variability of responses to antithrombotic treatment among individuals (i.e., interindividual heterogeneity). Several factors have been identified in this interindividual heterogeneity in response to antithrombotic treatment. Pharmacogenetics has emerged as a field that identifies specific gene variants able to explain the variability in patient response to a given drug. Polymorphisms affecting the disposition, metabolism, transporters, or targets of a drug all can be implicated in the modification of an individual's antithrombotic drug response and therefore the safety and efficacy of the aforementioned drug. The present paper reviews the modulating role of different polymorphisms on individuals' responses to antithrombotic drugs commonly used in clinical practice.
Key Words: pharmacogenetics • polymorphism • antithrombotic therapy
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Abbreviations and Acronyms
| | ACS = acute coronary syndrome | | ADP = adenosine diphosphate | | COX = cyclooxygenase | | CYP = cytochrome P450 | | FXIII = factor XIII | | GP = glycoprotein | | HIT = heparin-induced thrombocytopenia | | HR = hazard ratio | | INR = international normalized ratio | | LMWH = low molecular weight heparin | | MDR = multidrug resistance-associated protein | | MI = myocardial infarction | | PCI = percutaneous coronary intervention | | VKA = vitamin K antagonist | | VKOR
= vitamin K epoxide reductase | | VKORC1
= vitamin K epoxide reductase subunit 1 |
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