Adrenergic receptor polymorphisms and platelet reactivity after treatment with dual antiplatelet therapy with aspirin and clopidogrel in acute coronary syndrome

作者：Cuisset Thomas; Hamilos Michalis; Delrue Leen; Frere Corinne; Verhamme Katia; Bartunek Jozef; Saut Noemie; Bonnet Jean Louis; Eijgelsheim Mark; Wijns William; Alessi Marie Christine; Barbato Emanuele^*

来源：Thrombosis and Haemostasis, 2010, 103(4): 774-779.

DOI：10.1160/TH09-06-0355

• Antiplatelet agents
• coronary syndrome
• single nucleotide polymorphisms

Platelet response to clopidogrel shows inter-individual variability that is partially explained by genetic polymorphisms. This variability affects clinical outcome when clopidogrel is administered in patients with acute coronary syndrome (ACS). Catecholamines, released during ACS, contribute to platelet aggregation through platelet alpha(2A)- (alpha(2A)-AR) and beta(2)-adrenergic receptor (beta(2)-AR) stimulation. It was the objective of this study to assess the potential influence of a2A-AR and beta(2)-AR gene polymorphisms on platelet reactivity after dual antiplatelet therapy with aspirin and clopidogrel in ACS. We screened 641 ACS patients for 6.3/6.7 kb alpha(2A)-AR polymorphism, and for Arg16Gly and Gln27Glu beta(2)-AR polymorphism. After 600 mg clopidogrel, we assessed ADP 10 mu mol-induced platelet aggregation (ADP-Ag) and vasoactive stimulated phosphoprotein (VASP). All single nucleotide polymorphisms were in Hardy-Weinberg equilibrium. A slight though negligible association was found between 6.3 kb allele of alpha(2A)-AR with platelet reactivity ADP-Ag induced (beta: -2.91 [-5.68;-0.14], p=0.04). A borderline not significant reduction in PRI VASP was observed in 6.3 kb alpha(2A)-AR carriers (beta: -3.81 [-0.09;7.72], p=0.06). No significant effect on platelet parameters was observed for the other tested polymorphisms. Common alpha(2A)- and beta(2)-adrenergic receptor polymorphisms do not show any major impact on residual platelet reactivity in non-ST-elevation ACS when a dual antiplatelet therapy with 250 mg aspirin and 600 mg clopidogrel is administered.

• 出版日期2010-4