Lack of association between the 807 C/T polymorphism of glycoprotein Ia gene and post-treatment platelet reactivity after aspirin and clopidogrel in patients with acute coronary syndrome.
Variability in platelet response to antiplatelet therapy and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. It was the aim of the present study to assess whether the response to aspirin and clopidogrel may be influenced by the 807 C/T polymorphism of the glycoprotein Ia (GpIa) gene in patients with non-ST elevation acute coronary syndrome (NSTE ACS). Six hundred one NSTE ACS patients were included in our study and were divided into three groups: CC homozygotes, CT heterozygotes ad TT homozygotes. All patients received loading doses of 600 mg clopidogrel and 250 mg aspirin at least 12 hours before blood samples were drawn. Post-treatment platelet reactivity was assessed by post treatment ADP 10 microM-induced platelet aggregation (ADP-Ag), VASP phosphorylation (PRI VASP) and P-selectin expression. Non-response to dual antiplatelet therapy was defined by high post-treatment platelet reactivity (HPPR=ADP-Ag > 70%). Significant variability in the distribution of platelet parameters was observed in the overall study population. No significant difference in platelet parameters profiles was observed within patients having the same genotype, for ADP-Ag (p=0.33), PRIVASP (p=0.72) and P-selectin expression (p=0.37). The genotype frequencies of the 807 C/T polymorphism of the GpIa gene were similar in responders and non-responders defined by persistent HPPR (p=0.104). In conclusion, our study did not show any influence of 807 C/T polymorphism of GpIa gene on post-treatment platelet reactivity assessed by ADP-Ag, PRI VASP or P-selectin expression in 601 NSTE ACS patients.
Cuisset
Thomas
T
Department of cardiology, CHU Timone, Marseille, France.
Frere
Corinne
C
Quilici
Jacques
J
Morange
Pierre-Emmanuel
PE
Saut
Noémie
N
Romero-Barra
Marie
M
Camoin
Laurence
L
Lambert
Marc
M
Juhan-Vague
Irène
I
Bonnet
Jean-Louis
JL
Alessi
Marie-Christine
MC
D000208:Acute Disease; D000244:Adenosine Diphosphate; D000368:Aged; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000077144:Clopidogrel; D003596:Cytosine; D005260:Female; D005602:France; D005838:Genotype; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D019007:P-Selectin / Q000032:analysis; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010979:Platelet Function Tests; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D013577:Syndrome; D013941:Thymine; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D039421:Integrin alpha2; D008840:Microfilament Proteins; D019007:P-Selectin; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D003596:Cytosine; D000077144:Clopidogrel; D013988:Ticlopidine; D013941:Thymine; D001241:Aspirin