Skip to main content

Platelet glycoprotein IIIA PIA2 polymorphism is associated with ST elevation acute myocardial infarction in young Mexican population

Journal of Thrombosis and Thrombolysis volume 33, pages 389–396 (2012)Cite this article

Abstract

Platelet membrane glycoprotein IIb/IIIa plays an important role in adhesion and platelet aggregation. Polymorphisms of genes in platelet activation and fibrinolysis have been associated with myocardial infarction (MI), however this has not been confirmed by others, and results are still controversial. The aim of this study was to determine the frequency distribution and association of polymorphism in the platelet glycoprotein GPIIIa PLA/A2 and the possible interaction with the 4G/5G in the plasminogen activator inhibitor genes with ST elevation acute myocardial infarction (STEAMI) in young Mexican subjects. A total of 254 unrelated patients with first STEAMI ≤45 years of age, who were admitted to a cardiovascular intense care unit and 254 healthy controls matched by age and gender were recruited from January 2006 and May 2011. The PIA1/A2 and 4G/5G polymorphism were determined in all participants by a PCR restriction based restriction endonuclease digestion. There was a difference in the PIA2 allele distribution between both groups (P = 0.001). Also, we found an increased percent of 4G allele in the group of patients compared to control group (P = 0.001). There was an increased risk for STEAMI in carries with the allele PIA2 and 4G (OR = 4.3, CI 95 % 1.7–6.5). The modifiable risk factors such: smoking, hypertension, family history of cardiovascular disease, and dyslipidemia were associated with myocardial infarction. This is the first study to evaluate the role of gene polymorphism in both the thrombotic and fibrinolytic pathways in young Mexican individuals with STEAMI and suggest a synergistic effect between PIA2 and 4G allele.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Yusuf S, S Hawken, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L, INTERHEART Study Investigators (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364:937–952

    Google Scholar 

  2. Instituto Nacional de Estadística, Geografía e Informática. Censo Nacional de Población y Vivienda (2007) México. http://www.inegi.org.mx

  3. Voetsch B, Loscalzo J (2004) Genetic determinants of arterial thrombosis. Arterioscler Thromb Vasc Biol 24:216–229

    PubMed  Article  CAS  Google Scholar 

  4. Lefkovits J, Plow EF, Topol EJ (1995) Platelet glycoprotein IIb/IIIa receptors in cardiovascular meicine. N Eng J Med 33:1159–1553

    Google Scholar 

  5. Feng D, Lindpaintner K, Larson MG, Rao VS, O’Donnell CJ, Lipinska I, Schmitz C, Sutherland PA, Silbershatz H, D’Agostino RB, Muller JE, Myers RH, Levy D, Tofler GH (1999) Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham offspring study. Arterioscler Thromb Vasc Biol 19:1142–1147

    PubMed  Article  CAS  Google Scholar 

  6. Vijayan KV, Liu Y, Dong JF, Bray PF (2003) Enhanced activation of mitogen-activated protein kinase and myosin light chain kinase by the Pro33 polymorphism of integrin beta 3. J Biol Chem 278:3860–3867

    PubMed  Article  CAS  Google Scholar 

  7. Newman PJ, Derbes RS, Aster RH (1989) The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J Clin Invest 83:1778–1781

    PubMed  Article  CAS  Google Scholar 

  8. Kastrati A, Schömig A, Seyfarth M, Koch W, Elezi S, Böttiger C, Mehilli J, Schömig K, von Beckerath N (1999) PIA polymorphism of platelet glycoprotein IIIa and risk of restenosis after coronary stent placement. Circulation 99:1005–1010

    PubMed  CAS  Google Scholar 

  9. Walter DH, Schächinger V, Elsner M, Dimmeler S, Zeiher AM (1997) Platelet glycoprotein IIIa polymorphism and risk of coronary stent thrombosis. Lancet 350:1217–1219

    PubMed  Article  CAS  Google Scholar 

  10. Zotz RB, Klein M, Dauben HP, Moser C, Gams E, Scharf RE (2000) Prospective analysis after coronary-artery bypass grafting: platelet GP IIIa polymorphism (HPA-1b/PIA2) is a risk factor for bypass occlusion, myocardial infarction, and death. Thromb Haemost 83:404–407

    PubMed  CAS  Google Scholar 

  11. 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 2:214–217

    Google Scholar 

  12. Anderson JL, King GJ, Bair TL, Elmer SP, Muhlestein JB, Habashi J, Carlquist JF (1999) Associations between a polymorphism in the gene encoding glycoprotein IIIa and myocardial infarction or coronary artery disease. J Am Coll Cardiol 33:727–733

    PubMed  Article  CAS  Google Scholar 

  13. Grove EL, Ørntoft TF, Lassen JF, Jensen HK, Kristensen SD (2004) The platelet polymorphism PlA2 is a genetic risk factor for myocardial infarction. J Intern Med 255:637–644

    PubMed  Article  CAS  Google Scholar 

  14. Galasso G, Santulli G, Piscione F, De Rosa R, Trimarco V, Piccolo R, Cassese S, Iaccarino G, Trimarco B, Chiariello M (2010) The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events. BMC Cardiovasc Disord 16(10):41

    Article  Google Scholar 

  15. 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

    PubMed  Article  CAS  Google Scholar 

  16. Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K (1997) A1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet 349:385–388

    PubMed  Article  CAS  Google Scholar 

  17. Samani NJ, Lodwick D (1997) Glycoprotein IIIa polymorphism and risk of myocardial infarction. Cardiovasc Res 33:693–697

    PubMed  Article  CAS  Google Scholar 

  18. 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

    PubMed  Article  CAS  Google Scholar 

  19. Tschoepe D, Menart B, Ferber P, Altmann C, Haude M, Haastert B, Roesen P (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

    PubMed  Article  CAS  Google Scholar 

  20. Lagercrantz J, Bergman M, Lundman P, Tornvall P, Hjemdahl P, Hamsten A, Eriksson P (2003) No evidence that the PLA1/PLA2 polymorphism of platelet glycoprotein IIIa is implicated in angiographically characterized coronary atherosclerosis and premature myocardial infarction. Blood Coagul Fibrinolysis 14:749–753

    PubMed  Article  CAS  Google Scholar 

  21. Sentí M, Aubó C, Bosch M, Pavesi M, Pena A, Masiá R, Marrugat J (1998) Platelet glycoprotein IIb/IIIa genetic polymorphism is associated with plasma fibrinogen levels in myocardial infarction patients. The REGICOR Investigators. Clin Biochem 31:647–651

    PubMed  Article  Google Scholar 

  22. Ardissino D, Mannucci PM, Merlini PA, Duca F, Fetiveau R, Tagliabue L, Tubaro M, Galvani M, Ottani F, Ferrario M, Corral J, Margaglione M (1999) Prothrombotic genetic risk factors in young survivors of myocardial infarction. Blood 94:46–51

    PubMed  CAS  Google Scholar 

  23. Mannucci PM, Bernardinelli L, Foco L, Galli M, Ribichini F, Tubaro M, Peyvandi F (2005) Tissue plasminogen activator antigen is strongly associated with myocardial infarction in young women. J Thromb Haemost 3:280–286

    PubMed  Article  CAS  Google Scholar 

  24. Huber K (2001) Plasminogen activator inhibitor type-1 (part one): basic mechanisms, regulation, and role for thromboembolic disease. J Thromb Thrombolysis 11:183–193

    PubMed  Article  CAS  Google Scholar 

  25. Dawson S, Hamsten A, Wiman B, Henney A, Humphries S (1991) Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity. Arterioscler Thromb 11:183–190

    PubMed  Article  CAS  Google Scholar 

  26. Onalan O, Balta G, Oto A, Kabakci G, Tokgozoglu L, Aytemir K, Altay C, Gurgey A, Nazli N (2008) Plasminogen activator inhibitor-1 4G4G genotype is associated with myocardial infarction but not with stable coronary artery disease. J Thromb Thrombolysis 26:211–217

    PubMed  Article  CAS  Google Scholar 

  27. Rallidis LS, Gialeraki A, Merkouri E, Liakos G, Dagres N, Sionis D, Travlou A, Lekakis J, Kremastinos DT (2010) Reduced carriership of 4G allele of plasminogen activator inhibitor-1 4G/5G polymorphism in very young survivors of myocardial infarction. J Thromb Thrombolysis 29:497–502

    PubMed  Article  CAS  Google Scholar 

  28. Isordia-Salas I, Leaños-Miranda A, Sainz IM, Reyes-Maldonado E, Borrayo-Sánchez G (2009) Association of the plasminogen activator inhibitor-1 gene 4G/5G polymorphism with ST elevation acute myocardial infarction in young patients. Rev Esp Cardiol 62:365–372

    PubMed  Article  Google Scholar 

  29. 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. J Am Coll Cardiol 36:959–969

    PubMed  Article  CAS  Google Scholar 

  30. Ferguson JL, Beckett GJ, Stoddart M, Walker SW, Fox KA (2000) Myocardial infarction redefined: The new ACC/ESC definition, based on cardiac troponin, increases the apparent incidence of infarction. Heart 88:343–347

    Article  Google Scholar 

  31. US Department of Health and Human Services, National High Blood Pressure Education Program, The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (2003). NIH Publication No. 03-5233. NIH

  32. American Diabetes Association/American College of Cardiology (2002) Diabetic dyslipidemia http://www.diabetes.org/uedocuments/ADACardioReview3

  33. American Diabetes Association (2005) Diagnosis and classification of diabetes mellitus. Diabetes Care 8:S37–S42

    Article  Google Scholar 

  34. Borrayo-Sánchez G, Madrid-Miller A, Arriaga-Nava R, Ramos-Corrales MA, García-Aguilar J, Almeida-Gutiérrez E (2010) Risk stratified in the national registry of acute coronary syndromes at the IMSS. Rev Med Inst Mex Seguro Soc 48:259–264

    PubMed  Google Scholar 

  35. Pegoraro RJ, Ranjith N (2005) Plasminogen activator inhibitor type 1 (PAI-1) and platelet glycoprotein IIIa (PGIIIa) polymorphisms in young Asian Indians with acute myocardial infarction. Cardiovasc J S Afr 16:266–270

    PubMed  CAS  Google Scholar 

  36. 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

    PubMed  Article  CAS  Google Scholar 

  37. Boekholdt SM, Peters RJ, de Maat MP, Zwinderman AH, van Der Wall EE, Reitsma PH, Jukema JW, Kastelein JJ (2004) Interaction between a genetic variant of the platelet fibrinogen receptor and fibrinogen levels in determining the risk of cardiovascular events. Am Heart J 147:181–186

    PubMed  Article  CAS  Google Scholar 

  38. Bojesen SE, Juul K, Schnohr P, Tybjaerg-Hansen A, Nordestgaard BG, Copenhagen City Heart Study (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

    Google Scholar 

  39. Benze G, Heinrich J, Schulte H, Rust S, Nowak-Göttl U, Tataru MC, Köhler E, Assmann G, Junker R (2002) Association of the GPIa C807T and GPIIIa PlA1/A2 polymorphisms with premature myocardial infarction in men. Eur Heart J 23:325–330

    PubMed  Article  CAS  Google Scholar 

  40. Wiwanitkit V (2006) PIA1/A2 polymorphism of the platelet glycoprotein receptor IIb/IIIIa and its correlation with myocardial infarction: an appraisal. Clin Appl Thromb Hemost 12:93–95

    PubMed  Article  CAS  Google Scholar 

  41. Zhu MM, Weedon J, Clark LT (2000) Meta-analysis of the association of platelet glycoprotein IIIa PlA1/A2 polymorphism with myocardial infarction. Am J Cardiol 86:1000–1005

    PubMed  Article  CAS  Google Scholar 

  42. Scaglione L, Bergerone S, Gaschino G, Imazio M, Maccagnani A, Gambino R, Cassader M, Di Leo M, Macchia G, Brusca A, Pagano G, Cavallo-Perin P (1998) Lack of relationship between the P1A1/P1A2 polymorphism of platelet glycoprotein IIIa and premature myocardial infarction. Eur J Clin Invest 28:385–388

    PubMed  Article  CAS  Google Scholar 

  43. Pontiggia L, Lassila R, Pederiva S, Schmid HR, Burger M, Beer JH (2002) Increased platelet-collagen interaction associated with double homozygosity for receptor polymorphisms of platelet GPIa and GPIIIa. Arterioscler Thromb Vasc Biol 22:2093–2098

    PubMed  Article  CAS  Google Scholar 

  44. Pontiggia L, Lassila R, Pederiva S, Schmid HR, Burger M, Beer JH (2002) Acute myocardial infarction in the young—the University of Michigan experience. Am Heart J 143:56–62

    Article  Google Scholar 

  45. Rott D, Leibowitz D, Finci-Yeheskel Z, Barak V, Chajek- Shaul T, Weiss T, Levin M, Urieli- Shoval S (2009) The relation of plasminogen activator inhibitor-1 levels the ST deviation pattern of acute myocardial infarction. Cardiology 112:56–59

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by El Fondo de Investigación en Salud IMSS grant (FIS/IMSS/PROT/G09/748) by CONACyT (Consolidación de Grupos de Investigación modalidad repatriación No. 050232), and Apoyo Complementario para Investigadores Nivel 1 No. 118254 (to Dr. Isordia).

Conflict of interest

None declared.

Author information

Affiliations

  1. Unidad de Investigación Médica en Trombosis, Hemostasia y Aterogénesis, H.G.R. No 1. Dr. “Carlos Mac Gregor Sánchez Navarro” Instituto Mexicano del Seguro Social, Mexico, DF, Mexico

    David Santiago-Germán, Abraham Majluf-Cruz & Irma Isordia-Salas

  2. Escuela de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico, DF, Mexico

    David Santiago-Germán & Ethel García-Latorre

  3. Unidad de Investigación Médica en Medicina Reproductiva, UMAE HGO 4, Instituto Mexicano del Seguro Social, Mexico, DF, Mexico

    Alfredo Leaños-Miranda

  4. Hospital de Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Unidad de Cuidados Intensivos Cardiovasculares, Mexico, DF, Mexico

    Gabriela Borrayo-Sánchez

  5. Coahuila No. 5, Apartado Postal B 32, Mexico, DF, CP 06703, Mexico

    Irma Isordia-Salas

Authors
  1. David Santiago-Germán
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alfredo Leaños-Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ethel García-Latorre
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriela Borrayo-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abraham Majluf-Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Irma Isordia-Salas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Irma Isordia-Salas.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Santiago-Germán, D., Leaños-Miranda, A., García-Latorre, E. et al. Platelet glycoprotein IIIA PIA2 polymorphism is associated with ST elevation acute myocardial infarction in young Mexican population. J Thromb Thrombolysis 33, 389–396 (2012). https://doi.org/10.1007/s11239-012-0714-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-012-0714-x

Keywords

  • Atherothrombosis
  • Myocardial infarction
  • Glycoprotein
  • PIA1/A2 polymorphism
  • PAI-1