Aspirin Resistance and its Genetics

Genetics of Aspirin Variables Response

Abstract

Aspirin is among the most widely used efficient anti-platelet medications in the world for the management and reducing the risk of heart attacks and strokes in patients with atherothrombosis. Its pharmacodynamic effects are attained by permanently inhibiting the activation of platelet COX enzymes. This inhibition prevents the transformation of arachidonic acid (AA) into thromboxane A2 (TXA2), which effectively reduces platelet activation and aggregation. It is widely recognized that the platelet inhibition reaction to aspirin varies significantly among individuals. Some patients exhibit minimal reduction in platelet activity despite aspirin therapy and are classified as low responders, non-responders, or aspirin-resistant. Various allelic variants of the cyclooxygenase (COX) genes, along with several other genes are also involved in the pharmacokinetics and pharmacodynamics of aspirin. Research have shown that there is inter-individual variability in aspirin response ranging from mild to severe reduction which may be attributable to Single Nucleotide Polymorphism in genes responsible for aspirin metabolizing enzymes. This article reviews the mechanism of aspirin action, mechanism of aspirin resistance involving genetic polymorphisms in different aspirin metabolizing genes and its clinical impacts.