Advertisement

Role of glycoprotein Ia gene polymorphisms in determining platelet function in myocardial infarction patients undergoing percutaneous coronary intervention on dual antiplatelet treatment

  • Betti Giusti
    Correspondence
    Corresponding author. Tel.: +39 055 794 9420; fax: +39 055 794 9418.
    Affiliations
    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
    Search for articles by this author
  • Anna Maria Gori
    Affiliations
    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
    Search for articles by this author
  • Rossella Marcucci
    Affiliations
    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
    Search for articles by this author
  • Ilaria Sestini
    Affiliations
    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
    Search for articles by this author
  • Claudia Saracini
    Affiliations
    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
    Search for articles by this author
  • Rita Paniccia
    Affiliations
    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
    Search for articles by this author
  • Serena Poli
    Affiliations
    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
    Search for articles by this author
  • Cristina Giglioli
    Affiliations
    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
    Search for articles by this author
  • Serafina Valente
    Affiliations
    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
    Search for articles by this author
  • Domenico Prisco
    Affiliations
    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
    Search for articles by this author
  • Gian Franco Gensini
    Affiliations
    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
    Search for articles by this author
  • Rosanna Abbate
    Affiliations
    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
    Search for articles by this author

      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 μM 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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Buchanan M.R.
        • Brister S.J.
        Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically.
        Can J Cardiol. 1995; 11: 221-227
        • Eikelboom J.W.
        • Hirsh J.
        • Weitz J.I.
        • Johnston M.
        • Yi Q.
        • Yusuf S.
        Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events.
        Circulation. 2002; 105: 1650-1655
        • Gurbel P.A.
        • Bliden K.P.
        • Hiatt B.L.
        • O’Connor C.M.
        Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity.
        Circulation. 2003; 107: 2908-2913
        • Serebruany V.L.
        • Steinhubl S.R.
        • Berger P.B.
        • Malinin A.I.
        • Bhatt D.L.
        • Topol E.J.
        Variability in platelet responsiveness to clopidogrel among 544 individuals.
        J Am Coll Cardiol. 2005; 45: 246-251
        • Gum P.A.
        • Kottke-Marchant K.
        • Welsh P.A.
        • White J.
        • Topol E.J.
        A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease.
        J Am Coll Cardiol. 2003; 41: 961-965
        • Lev E.I.
        • Patel R.T.
        • Maresh K.J.
        • et al.
        Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance.
        J Am Coll Cardiol. 2006; 47: 27-33
        • Chen W.H.
        • Lee P.Y.
        • Ng W.
        • Tse H.F.
        • Lau C.P.
        Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary interventions despite clopidogrel pre-treatment.
        J Am Coll Cardiol. 2004; 43: 1122-1126
        • Chen W.H.
        • Lee P.Y.
        • Ng W.
        • et al.
        Relation of aspirin resistance to coronary flow reserve in patients undergoing elective percutaneous coronary intervention.
        Am J Cardiol. 2005; 96: 760-763
        • Wenaweser P.
        • Dorffler-Melly J.
        • Imboden K.
        • et al.
        Stent thrombosis is associated with an impaired response to antiplatelet therapy.
        J Am Coll Cardiol. 2005; 45: 1748-1752
        • Ajzenberg N.
        • Aubry P.
        • Huisse M.G.
        • et al.
        Enhanced shear-induced platelet aggregation in patients who experience subacute stent thrombosis.
        J Am Coll Cardiol. 2005; 45: 1753-1756
        • Marcucci R.
        • Paniccia R.
        • Antonucci E.
        • et al.
        Usefulness of aspirin resistance after percutaneous coronary intervention for acute myocardial infarction in predicting one-year major adverse coronary events.
        Am J Cardiol. 2006; 96: 1156-1159
        • Clemetson K.J.
        • Clemetson J.M.
        Platelet collagen receptors.
        Thromb Haemost. 2001; 86: 189-197
        • Jung S.M.
        • Moroi M.
        Platelets interact with soluble and insoluble collagens through characteristically different reactions.
        J Biol Chem. 1998; 273: 14827-14837
        • Verkleij M.W.
        • Morton L.F.
        • Knight C.G.
        • de Groot P.G.
        • Barnes M.J.
        • Sixma J.J.
        Simple collagen-like peptides support platelet adhesion under static but not under flow conditions: interaction via alpha2 beta1 and von Willebrand factor with specific sequences in native collagen is a requirement to resist shear forces.
        Blood. 1998; 91: 3808-3816
        • Santoro S.A.
        • Zutter M.M.
        The alpha 2 beta 1 integrin: a collagen receptor on platelets and other cells.
        Thromb Haemost. 1995; 74: 813-821
        • Sixma J.J.
        • van Zanten G.H.
        • Huizinga E.G.
        • et al.
        Platelet adhesion to collagen: an update.
        Thromb Haemost. 1997; 78: 434-438
        • Moroi M.
        • Jung S.M.
        • Shinmyozu K.
        • Tomiyama Y.
        • Ordinas A.
        • Diaz-Ricart M.
        Analysis of platelet adhesion to a collagen-coated surface under flow conditions: the involvement of glycoprotein VI in the platelet adhesion.
        Blood. 1996; 88: 2081-2092
        • Jung S.M.
        • Moroi M.
        Signal-transducing mechanisms involved in activation of the platelet collagen receptor integrin alpha(2)beta(1).
        J Biol Chem. 2000; 275: 8016-8026
        • Kunicki T.J.
        The influence of platelet collagen receptor polymorphisms in hemostasis and thrombotic disease.
        Arterioscler Thromb Vasc Biol. 2002; 22: 14-20
        • Corral J.
        • Gonzalez-Conejero R.
        • Rivera J.
        • Ortuno F.
        • Aparicio P.
        • Vicente V.
        Role of the 807 C/T polymorphism of the alpha2 gene in platelet GP Ia collagen receptor expression and function—effect in thromboembolic diseases.
        Thromb Haemost. 1999; 81: 951-956
        • Kritzik M.
        • Savage B.
        • Nugent D.J.
        • Santoso S.
        • Ruggeri Z.M.
        • Kunicki T.J.
        Nucleotide polymorphisms in the alpha2 gene define multiple alleles that are associated with differences in platelet alpha2 beta1 density.
        Blood. 1998; 92: 2382-2388
        • Angiolillo D.J.
        • Fernandez-Ortiz A.
        • Bernardo E.
        • et al.
        807 C/T Polymorphism of the glycoprotein Ia gene and pharmacogenetic modulation of platelet response to dual antiplatelet treatment.
        Blood Coagul Fibrinolysis. 2004; 15: 427-433
        • Angiolillo D.J.
        • Fernandez-Ortiz A.
        • Bernardo E.
        • et al.
        Variability in platelet aggregation following sustained aspirin and clopidogrel treatment in patients with coronary heart disease and influence of the 807 C/T polymorphism of the glycoprotein Ia gene.
        Am J Cardiol. 2005; 96: 1095-1099
        • Frusconi S.
        • Giusti B.
        • Rossi L.
        • et al.
        Improvement of low-density microelectronic array technology to characterize 14 mutations/single-nucleotide polymorphisms from several human genes on a large scale.
        Clin Chem. 2004; 50: 775-777
        • Reiner A.P.
        • Aramaki K.M.
        • Teramura G.
        • Gaur L.
        Analysis of platelet glycoprotein Ia (alpha2 integrin) allele frequencies in three North American populations reveals genetic association between nucleotide 807C/T and amino acid 505 Glu/Lys (HPA-5) dimorphisms.
        Thromb Haemost. 1998; 80: 449-456
        • Moshfegh K.
        • Wuillemin W.A.
        • Redondo M.
        • et al.
        Association of two silent polymorphisms of platelet glycoprotein Ia/IIa receptor with risk of myocardial infarction: a case–control study.
        Lancet. 1999; 353: 351-354
      1. Casorelli I, De Stefano V, Leone AM, et al. The C807T/G873A polymorphism in the platelet glycoprotein Ia gene and the risk of acute coronary syndrome in the Italian population. Br J Haematol; 114: 150–4.

        • Antoniades C.
        • Tousoulis D.
        • Vasiliadou C.
        • Stefanadi E.
        • Marinou K.
        • Stefanadis C.
        Genetic polymorphisms of platelet glycoprotein Ia and the risk for premature myocardial infarction: effects on the release of sCD40L during the acute phase of premature myocardial infarction.
        J Am Coll Cardiol. 2006; 47: 1959-1966
        • Savage B.
        • Ginsberg M.H.
        • Ruggeri Z.M.
        Influence of fibrillar collagen structure on the mechanisms of platelet thrombus formation under flow.
        Blood. 1999; 94: 2704-2715
        • Jacquelin B.
        • Tarantino M.D.
        • Kritzik M.
        • et al.
        Allele-dependent transcriptional regulation of the human integrin alpha2 gene.
        Blood. 2001; 97: 1721-1726
        • Santoso S.
        • Kunicki T.J.
        • Kroll H.
        • Haberbosch W.
        • Gardemann A.
        Association of the platelet glycoprotein Ia C807T gene polymorphism with nonfatal myocardial infarction in younger patients.
        Blood. 1999; 93: 2449-2453
        • Carlsson L.E.
        • Santoso S.
        • Spitzer C.
        • Kessler C.
        • Greinacher A.
        The alpha2 gene coding sequence T807/A873 of the platelet collagen receptor integrin alpha2beta1 might be a genetic risk factor for the development of stroke in younger patients.
        Blood. 1999; 93: 3583-3586