title: Role of glycoprotein Ia gene polymorphisms in determining platelet function in myocardial infarction patients undergoing percutaneous coronary intervention on dual antiplatelet treatment.
abstract: Response variability to antiplatelet treatment has been described and the widespread use of acetylsalicylic acid (ASA) and clopidogrel requires clarification of the residual platelet reactivity (RPR). Various glycoprotein Ia (GpIa) polymorphisms have been investigated, but their influence on platelet reactivity in myocardial infarction (MI) patients undergoing percutaneous coronary intervention (PCI) on dual antiplatelet treatment is not still elucidated. Aim of this study was to evaluate the effect of C807T, G873A and T837C polymorphisms of GpIa on modulating platelet function in MI patients on dual antiplatelet treatment undergoing PCI. We measured platelet function by both a point-of-care assay (PFA100) and platelet-rich-plasma aggregation in 289 MI patients undergoing PCI and receiving dual antiplatelet treatment. Our data show that C807T/G873A polymorphisms, but not T837C, are associated with higher platelet reactivity. Carriers of the 807T/873A allele had significantly higher platelet aggregation values after arachidonic acid (AA) and collagen stimuli and, even if they did not reach the statistical significance, after 2 and 10 microM ADP stimuli; 807T/873A allele carriers had also significantly shorter closure times on PFA100/epinephrine membranes. At the multiple analyses, C807T/G873A polymorphisms resulted an independent risk factor for RPR defined by both AA induced platelet aggregation (OR=3.0, 95%CI 1.17-7.89, p=0.022) or by PFA100/epinephrine (OR=4.1, 95%CI 1.53-10.89, p=0.005). In conclusion, this study shows the 807T/873A allele of the GpIa gene is an independent risk factor for the RPR on dual antiplatelet treatment, and extends, in a larger acute coronary syndrome population, the observation that the 807T/873A allele is associated with higher platelet reactivity.
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy. Electronic address: betti.giusti@unifi.it.
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Gori
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Sestini
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Saracini
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Paniccia
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Poli
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Giglioli
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Serafina
authors.initials: S
authors.lastname: Valente
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Prisco
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy; Centro S. Maria agli Ulivi, Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy.
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
authors.affiliation: Department of Medical and Surgical Critical Care and Center of Research, Transfer and High Education, "DENOTHE", University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000502:physiology; D015331:Cohort Studies; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D039421:Integrin alpha2 / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000628:therapy; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D039421:Integrin alpha2; D010975:Platelet Aggregation Inhibitors