Title:Pharmacogenetics of the Antiplatelet Effect of Aspirin
Volume: 18
Issue: 33
Author(s): Morten Wurtz, Steen Dalby Kristensen, Anne-Mette Hvas and Erik Lerkevang Grove
Affiliation:
Keywords:
Aspirin, genetic testing, pharmacogenetics, platelet glycoprotein IIb-IIIa complex, platelet aggregation inhibitors, platelet function
tests, polymorphisms
Abstract: The concept of "pharmacogenetics" addresses genetically determined variation in how individuals respond to drugs. Accordingly,
specific genetic variants have been suggested as contributors to a reduced response to various antiplatelet drugs. Aspirin is a cornerstone
in secondary cardiovascular prevention and has been thoroughly investigated. The efficacy of aspirin is well documented, although
with considerable interindividual variation. According to meta-analyses, a reduced antiplatelet effect of aspirin confers an increased
risk of cardiovascular events. The platelet response to aspirin is assessed by in vitro evaluation of thromboxane-dependent platelet
function. A reduced antiplatelet effect of aspirin can be explained by several mechanisms, which are largely determined by clinical,
pharmacodynamic, biological and genetic factors. During the past decade, numerous studies have identified genetic polymorphisms significantly
associated with cardiovascular events and modulating the antiplatelet effect of aspirin. However, results have been contradictory
allowing only few firm conclusions to be drawn. Polymorphisms in genes encoding glycoproteins (IIb/IIIa, Ia/IIa, VI and Ib), cyclooxygenases
(1 and 2), adenosine diphosphate receptors (P2Y1 and P2Y12) and proteins of importance for haemostasis (thromboxane A2
receptor, coagulation factor XIII, etc.) have been investigated. In particular, a polymorphism in the gene encoding glycoprotein IIb/IIIa
has been associated with a reduced antiplatelet effect of aspirin.
The additive value of an individual’s genetic makeup in predicting the antiplatelet effect of aspirin and the risk of cardiovascular events
remains controversial. The present review outlines the pharmacology of aspirin and provides an overview of specific genetic variations
considered to influence the antiplatelet effect of aspirin.