Adrenergic receptor polymorphisms and platelet reactivity after treatment with dual antiplatelet therapy with aspirin and clopidogrel in acute coronary syndrome.
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 alpha2A-(alpha2A-AR) and beta2-adrenergic receptor (beta2-AR) stimulation. It was the objective of this study to assess the potential influence of alpha2A-AR and beta2-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 alpha2A-AR polymorphism, and for Arg16Gly and Gln27Glu beta2-AR polymorphism. After 600 mg clopidogrel, we assessed ADP 10 micromol-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 alpha2A-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 alpha2A-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 alpha2A- and beta2-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.
Département de Cardiologie, CHU Timone, Marseille, France.
Thomas
T
Cuisset
Michalis
M
Hamilos
Michalis
M
Delrue
Corinne
C
Frère
Katia
K
Verhamme
Jozef
J
Bartunek
Noemie
N
Saut
Jean Louis
JL
Bonnet
Mark
M
Eijgelsheim
William
W
Wijns
Marie-Christine
MC
Alessi
Emanuele
E
Barbato
D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D000244:Adenosine Diphosphate; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000097:blood; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D010641:Phenotype; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects* / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
C547768:ADRA2A protein, human; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin