Abstract
A PlA1/A2 polymorphism of glycoprotein IIIa is known to be involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The aim of this study was to investigate an association between the PlA1/A2 polymorphism of the glycoprotein IIIa gene and the risk of MI in Caucasians with type 2 diabetes. 549 Caucasians with type 2 diabetes were enrolled in the cross sectional retrospective case–control study: 224 patients with MI and 325 diabetic subjects without CAD. Blood biochemical analysis was performed. The polymerase chain reaction with restriction fragment length polymorphism was used for genetic analysis. Patients with MI were older (62 ± 11.8 vs. 58.5 ± 11.6 years; P < 0.001), and had a longer duration of type 2 diabetes (17.6 ± 8.9 vs. 15.1 ± 9.2; P = 0.01) compared to the diabetics without CAD. A significant difference in distribution of the A2A2 genotype of glycoprotein IIIa was not found between 224 diabetic patients with MI in comparison to 325 diabetics without CAD (11.6 vs. 14,1 %; n.s.). The diabetes duration and male sex were independent factors for the development of MI, whereas the PlA1/A2 polymorphism of glycoprotein IIIa was not. To conclude, The A2A2 genotype of the glycoprotein IIIa polymorphism was not associated with MI risk in Caucasians with type 2 diabetes.
Similar content being viewed by others
References
Kozieradzka A, Kamiński K, Pepiński W et al (2007) The association between type 2 diabetes mellitus and A1/A2 polymorphism of glycoprotein IIIa gene. Acta Diabetol 44:30–33
Rozalski M, Boncler M, Luzak B, Watala C (2005) Genetic factors underlying differential blood platelet sensitivity to inhibitors. Pharmacol Rep 57:1–13
Coller BS, Shattil SJ (2008) The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood 112:3011–3025
Oki T, Kitaura J, Eto K et al (2006) Integrin alphaIIbbeta3 induces the adhesion and activation of mast cells through interaction with fibrinogen. J Immunol 176:52–60
Shattil SJ, Newman PJ (2004) Integrins: dynamic scaffolds for adhesion and signalling in platelets. Blood 104:1606–1615
Calvete JJ (1995) On the structure and function of platelet integrin alpha IIb beta 3, the fibrinogen receptor. Proc Soc Exp Biol Med 208:346–360
Du X, Ginsberg MH (1997) Integrin alpha(IIb)beta(3) and platelet function. Thromb Haemost 78:96–100
Wang R, Newman PJ (1998) Adhesive and signaling properties of a naturally occurring allele of glycoprotein IIIa with an amino acid substitution within the ligand binding domain-the Pena/Penb platelet alloantigenic epitopes. Blood 92:3260–3267
Bajt ML, Loftus JC (1994) Mutation of a ligand binding domain of beta 3 integrin. Integral role of oxygenated residues in alpha IIb beta 3 (GPIIb-IIIa) receptor function. J Biol Chem 269:20913–20919
Zotz RB, Deitenbeck R, Rehfeld ISB et al (1997) Increased platelet sensitivity related to GPIIIa polymorphism (HPA-b/PLA2). Circulation 96:664–665
Feng D, Lindpaintner K, Larson MG et al (1999) Increased platelet aggregability associated with platelet GpIIIa PlA2 polymorphism. The Framingham Offspring Study. Arterioscler Thromb Vasc Biol 19:1142–1147
Michelson AD, Furman MI, Goldschmidt-Clermont P et al (2000) Platelet GP IIIa PlA polymorphisms display different sensitivities to agonists. Circulation 101:1013–1018
Cooke GE, Liu-Stratton Y, Ferketich AK et al (2006) Effect of platelet antigen polymorphism on platelet inhibition by aspirin, clopidogrel, or their combination. J Am Coll Cardiol 47:541–546
Szczeklik A, Undas A, Sanak M et al (2000) Relationship between bleeding time, aspirin, and the PlA1/A2 polymorphism of platelet glycoprotein IIIa. Br J Haematol 110:965–967
Harris F, Chatfield L, Singh J, Phoenix DA (2004) Role of calpains in diabetes mellitus: a mini review. Mol Cell Biochem 261:161–167
Tschoepe D, Menart B, Ferber P et al (2003) Genetic variation of the platelet-surface integrin GPIIb-IIIa (PIA1/A2-SNP) shows a high association with type 2 diabetes mellitus. Diabetologia 46:984–989
März W, Boehm BO, Winkelmann BR, Hoffmann MM, Ludwigshafen Risk and Cardiovascular Health study (2004) The PlA1/A2 polymorphism of platelet glycoprotein IIIa is not associated with the risk of type 2 diabetes. The Ludwigshafen Risk and Cardiovascular Health Study. Diabetologia 47:1969–1973
Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K (1997) PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet 349:385–388
Bojesen SE, Juul K, Schnohr P, City Heart Study et al (2003) Platelet glycoprotein IIb/IIIa Pl(A2)/Pl(A2) homozygosity associated with risk of ischemic cardiovascular disease and myocardial infarction in young men: the Copenhagen City Heart Study. J Am Coll Cardiol 42:661–667
Grove EL, Orntoft TF, Lassen JF et al (2004) The platelet polymorphism PlA2 is a genetic risk factor for myocardial infarction. J Intern Med 255:637–644
Di Castelnuovo A, de Gaetano G, Donati MB et al (2001) Platelet glycoprotein receptor IIIa polymorphism PLA1/PLA2 and coronary risk: a meta-analysis. Thromb Haemost 85:626–633
Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, Weiss JL, Gerstenblith G, Goldschmidt-Clermont PJ (1996) A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 334:1090–1094
Burr D, Doss H, Cooke GE, Goldschmidt-Clermont PJ (2003) A meta-analysis of studies on the association of the platelet PlA polymorphism of glycoprotein IIIa and risk of coronary heart disease. Stat Med 22:1741–1760
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26(Suppl 1):S5–20
Alpert JS, Thygesen K, Antman E, Bassand JP (2000) Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. JACC 36:959–969
Mikkelsson J, Perola M, Penttilä A, Goldschmidt-Clermont PJ, Karhunen PJ (2001) The GPIIIa (beta3 integrin) PlA polymorphism in the early development of coronary atherosclerosis. Atherosclerosis 154:721–727
Garcia-Ribes M, Gonzalez-Lamuño D, Hernandez-Estefania R, Colman T, Pocovi M, Delgado-Rodriguez M, Garcia-Fuentes M, Revuelta JM (1998) Polymorphism of the platelet glycoprotein IIIa gene in patients with coronary stenosis. Thromb Haemost 79:1126–1129
Carter AM, Ossei-Gerning N, Wilson IJ, Grant PJ (1997) Association of the platelet Pl(A) polymorphism of glycoprotein IIb/IIIa and the fibrinogen Bbeta 448 polymorphism with myocardial infarction and extent of coronary artery disease. Circulation 96:1424–1431
Mamotte CD, van Bockxmeer FM, Taylor RR (1998) PIa1/a2 polymorphism of glycoprotein IIIa and risk of coronary artery disease and restenosis following coronary angioplasty. Am J Cardiol 82:13–16
Samani NJ, Lodwick D (1997) Glycoprotein IIIa polymorphism and risk of myocardial infarction. Cardiovasc Res 33:693–697
Gardemann A, Humme J, Stricker J, Nguyen QD, Katz N, Philipp M, Tillmanns H, Hehrlein FW, Rau M, Haberbosch W (1998) Association of the platelet glycoprotein IIIa PlA1/A2 gene polymorphism to coronary artery disease but not to nonfatal myocardial infarction in low risk patients. Thromb Haemost 80:214–217
Bottiger C, Kastrati A, Koch W et al (2000) HPA-1 and HPA-3 polymorphisms of the platelet fibrinogen receptor and coronary artery disease and myocardial infarction. Thromb Haemost 83:559–562
Gruchala M, Ciecwierz D, Ochman K et al (2003) Association between the Pl(A) platelet glycoprotein GPIIIa polymorphism and extent of coronary artery disease. Int J Cardiol 88:229–237
Pellitero S, Reverter JL, Tàssies D, Pizarro E, Monteagudo J, Salinas I, Aguilera E, Sanmartí A, Reverter JC (2010) Polymorphisms in platelet glycoproteins Ia and IIIa are associated with arterial thrombosis and carotid atherosclerosis in type 2 diabetes. Thromb Haemost 103:630–637
Pucci L, Lucchesi D, Fotino C, Grupillo M, Miccoli R, Penno G, Del Prato S (2003) Integrin Beta 3 PlA1/PlA2 polimorphism does not contribute to complications in both type 1 and type 2 diabetes. G Ital Nefrol 20:461–469
Oksala NK, Heikkinen M, Mikkelsson J et al (2007) Smoking and the platelet fibrinogen receptor glycoprotein IIb/IIIA PlA1/A2 polymorphism interact in the risk of lacunar stroke and midterm survival. Stroke 38:50–55
Colwell JA, Lopes-Virella MF (1988) A review of the development of large-vessel disease in diabetes mellitus. Am J Med 85(Suppl. 5):113A–118A
Elhadd TA, Kennedy G, Hill A et al (1999) Abnormal markers of endothelial cell activation and oxidative stress in children, adolescents and young adults with type 1 diabetes with no clinical vascular disease. Diabete Metab Res Rev 15:405–411
Bacci S, Villella M, Villella A, Langialonga T, Grilli M, Rauseo A, Mastroianno S, De Cosmo S, Fanelli R, Trischitta V (2002) Screening for silent myocardial ischaemia in type 2 diabetic patients with additional atherogenic risk factors: applicability and accuracy of the exercise stress test. Eur J Endocrinol 147:649–654
Maver A, Medica I, Peterlin B (2009) Search for sarcoidosis candidate genes by integration of data from genomic, transcriptomic and proteomic studies. Med Sci Monit 15:SR22–SR28
Acknowledgments
The authors thank Mrs. Visam Bajt, BA, for revising the English.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nikolajević-Starčević, J., Petrovič, D. The a1/a2 polymorphism of the glycoprotein IIIa gene and myocardial infarction in Caucasians with type 2 diabetes. Mol Biol Rep 40, 2077–2081 (2013). https://doi.org/10.1007/s11033-012-2265-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-012-2265-9