Download PDF
Thromb Haemost 2001; 85(04): 626-633
DOI: 10.1055/s-0037-1615644
Review Articles
Schattauer GmbH

Platelet Glycoprotein Receptor IIIa Polymorphism PlA1/PlA2 and Coronary Risk: a Meta-Analysis

Augusto Di Castelnuovo
1   “Angela Valenti” Laboratory of Genetic and Environmental Risk Factors for Thrombotic Disease, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Giovanni de Gaetano
1   “Angela Valenti” Laboratory of Genetic and Environmental Risk Factors for Thrombotic Disease, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Maria Benedetta Donati
1   “Angela Valenti” Laboratory of Genetic and Environmental Risk Factors for Thrombotic Disease, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Licia Iacoviello
1   “Angela Valenti” Laboratory of Genetic and Environmental Risk Factors for Thrombotic Disease, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
› Author Affiliations
Further Information

Publication History

Received 11 September 2000

Accepted after resubmission 13 November 2000

Publication Date:
08 December 2017 (online)

    Permissions and Reprints

Summary

Membrane glycoprotein IIb/IIIa plays a major role in platelet function. The gene encoding the glycoprotein IIIa shows a common polymorphism PlA1/PlA2 that was variably associated with vascular disease. To clarify the role of PlA1/PlA2 polymorphism in coronary risk, a meta-analysis of published data was conducted. Studies were identified both by MEDLINE searches, and hand searching of journals and abstract books.

A total of 34 studies for coronary artery disease (CAD), and 6 for restenosis after revascularization were identified, for a total of 9,095 cases and 12,508 controls. In CAD, the overall odds ratio for carriers of the PlA2 allele was 1.10 (95% CI: 1.03 to 1.18), and it was 1.21 (95% CI: 1.05 to 1.38) in subjects younger than 60. Overall odds ratio was 1.31 (95% CI: 1.10 to 1.56) after revascularization procedures.

The association of PlA2 status with overall cardiovascular disease in the general population is significant but weak; higher risk has been identified in less heterogeneous subgroups as in the younger cohorts and in the restenosis subset with stents.

Keywords

Coronary disease - genes - platelet glycoprotein - PlA1/PlA2 polymorphism - meta-analysis
 

  • References

  • 1 Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995; 332: 1553-9.
    CrossrefPubMedGoogle Scholar
  • 2 Nurden AT. Polymorphisms of human platelet membrane glycoproteins: structure and clinical significance. Thromb Haemost 1995; 74: 345-51.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Kunicki TJ, Newman PJ. The molecular immunology of human platelet proteins. Blood 1992; 80: 1386-404.
    PubMedGoogle Scholar
  • 4 Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, Weiss JL, Gerstenblith G, Goldschmidt-Clermont PJ. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 1996; 334: 1090-4.
    CrossrefPubMedGoogle Scholar
  • 5 Marian AJ, Brugada R, Kleiman NS. Platelet glycoprotein IIIa PlA polymorphism and myocardial infarction. N Engl J Med 1996; 335: 1071-2.
    CrossrefPubMedGoogle Scholar
  • 6 Carter AM, Ossei-Gerning N, Grant PJ. Platelet glycoprotein IIIa PlA polymorphism and myocardial infarction. N Engl J Med 1996; 335: 1072-3.
    PubMedGoogle Scholar
  • 7 Osborn SV, Hampton KK, Smillie D, Channer KS, Daly ME. Platelet glycoprotein IIIa gene polymorphism and myocardial infarction. Lancet 1996; 348: 1309-10.
    PubMedGoogle Scholar
  • 8 Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K. PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet 1997; 349: 385-8.
    CrossrefPubMedGoogle Scholar
  • 9 Carter AM, Ossei-Gerning N, Wilson IJ, Grant PJ. 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 1997; 96: 1424-31.
    CrossrefPubMedGoogle Scholar
  • 10 Herrmann SM, Poirier O, Marques-Vidal P, Evans A, Arveiler D, Luc G, Emmerich J, Cambien F. The Leu33/Pro polymorphism (PlA1/PlA2) of the glycoprotein IIIa (GPIIIa) receptor is not related to myocardial infarction in the ECTIM Study. Etude Cas-Temoins de l’Infarctus du Myocarde. Thromb Haemost 1997; 77: 1179-81.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Samani NJ, Lodwick D. Glycoprotein IIIa polymorphism and risk of myocardial infarction. Cardiovasc Res 1997; 33: 693-7.
    CrossrefPubMedGoogle Scholar
  • 12 Mamotte CD, van Bockxmeer FM, Taylor RR. PIa1/a2 polymorphism of glycoprotein IIIa and risk of coronary artery disease and restenosis following coronary angioplasty. Am J Cardiol 1998; 82: 13-6.
    PubMedGoogle Scholar
  • 13 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. Lack of relationship between the P1A1/P1A2 polymorphism of platelet glycoprotein IIIa and premature myocardial infarction. Eur J. Clin Invest 1998; 28: 385-8.
    CrossrefPubMedGoogle Scholar
  • 14 Carter AM, Mansfield MW, Grant PJ. Polymorphisms of platelet glyco-proteins in relation to macrovascular disease in type 2 diabetes mellitus. Diabet Med 1998; 15: 315-9.
    CrossrefPubMedGoogle Scholar
  • 15 Gardemann A, Humme J, Stricker J, Nguyen QD, Katz N, Philipp M, Tillmanns H, Hehrlein FW, Rau M, Haberbosch W. 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 1998; 80: 214-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Durante-Mangoni E, Davies GJ, Ahmed N, Ruggiero G, Tuddenham EG. Coronary thrombosis and the platelet glycoprotein IIIa gene PLA2 polymorphism. Thromb Haemost 1998; 80: 218-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Zotz RB, Winkelmann BR, Nauck M, Giers G, Maruhn-Debowski B, Marz W, Scharf RE. Polymorphism of platelet membrane glycoprotein IIIa: human platelet antigen 1b (HPA-1b/PlA2) is an inherited risk factor for premature myocardial infarction in coronary artery disease. Thromb Haemost 1998; 79: 731-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Garcia-Ribes M, Gonzalez-Lamuno D, Hernandez-Estefania R, Colman T, Pocovi M, Delgado-Rodriguez M, Garcia-Fuentes M, Revuelta JM. Polymorphism of the platelet glycoprotein IIIa gene in patients with coronary stenosis. Thromb Haemost 1998; 79: 1126-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Joven J, Simo JM, Vilella E, Camps J, Masana L, de Febrer G, Camprubi M, Richart C, Bardaji A, Casao E, Pocovi M, Civeira F. Lipoprotein (a) and the significance of the association between platelet glycoprotein IIIa polymorphisms and the risk of premature myocardial infarction. Atherosclerosis 1998; 140: 155-9.
    CrossrefPubMedGoogle Scholar
  • 20 Abbate R, Marcucci R, Camacho-Vanegas O, Pepe G, Gori AM, Capanni M, Simonetti I, Prisco D, Gensini GF. Role of platelet glycoprotein PL(A1/A2) polymorphism in restenosis after percutaneous transluminal coronary angioplasty. Am J Cardiol 1998; 82: 524-5.
    CrossrefPubMedGoogle Scholar
  • 21 Kekomaki S, Hamalainen L, Kauppinen-Makelin R, Palomaki H, Kaste M, Kontula K. Genetic polymorphism of platelet glycoprotein IIIa in patients with acute myocardial infarction and acute ischaemic stroke. J Cardiovasc Risk 1999; 6: 13-7.
    CrossrefPubMedGoogle Scholar
  • 22 Corral J, Gonzalez-Conejero R, Rivera J, Iniesta JA, Lozano ML, Vicente V. HPA-1 genotype in arterial thrombosis – role of HPA-1b polymorphism in platelet function. Blood Coagul Fibrinolysis 1997; 8: 284-90.
    CrossrefPubMedGoogle Scholar
  • 23 Bray PF, Cannon C, Goldschmidt-Clermont P, Moyé LA, Ochiai L, Pfeffer MA, Sacks FM, Braunwald E. The platelet PIA2 and ACE D allele polymorphisms are synergistic for the risk of recurrent events in patients post myocardial infarction and pravastatin reduces this risk. Blood 1998; 92 (Suppl. 01) 304a.
    PubMedGoogle Scholar
  • 24 Aleksic N, Juneja H, Folsom AR, Ahn C, Boerwinkle E, Chambless W, Wu KK. Prospective study of platelet PIA1/A2 polymorphism, platelet activation, and incidence of coronary heart disease. Blood 1998; 92 (Suppl. 01) 304a-5a.
    PubMedGoogle Scholar
  • 25 Grand’Maison A, Jacques L, Demers C, Marcoux S, Delage R. PECAM-1/CD31 and GPIIb/IIIa polymorphism and their roles in acute coronary thrombosis. Blood 1998; 92 (Suppl. 01) 190a.
    PubMedGoogle Scholar
  • 26 Senti M, Aubo C, Bosch M, Pavesi M, Pena A, Masia R, Marrugat J. Platelet glycoprotein IIb/IIIa genetic polymorphism is associated with plasma fibrinogen levels in myocardial infarction patients. The REGICOR Investigators. Clin Biochem 1998; 31: 647-51.
    CrossrefPubMedGoogle Scholar
  • 27 Laule M, Cascorbi I, Stangl V, Bielecke C, Wernecke KD, Mrozikiewicz PM, Felix SB, Roots I, Baumann G, Stangl K. A1/A2 polymorphism of glycoprotein IIIa and association with excess procedural risk for coronary catheter interventions: a case-controlled study. Lancet 1999; 353: 708-12.
    CrossrefPubMedGoogle Scholar
  • 28 Pastinen T, Perola M, Niini P, Terwilliger J, Salomaa V, Vartiainen E, Peltonen L, Syvanen A. Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population. Hum Mol Genet 1998; 7: 1453-62.
    CrossrefPubMedGoogle Scholar
  • 29 Anderson JL, King GJ, Bair TL, Elmer SP, Muhlestein JB, Habashi J, Carlquist JF. Associations between a polymorphism in the gene encoding glycoprotein IIIa and myocardial infarction or coronary artery disease. J Am Coll Cardiol 1999; 33: 727-33.
    CrossrefPubMedGoogle Scholar
  • 30 Ardissino D, Mannucci PM, Merlini PA, Duca F, Fetiveau R, Tagliabue L, Tubaro M, Galvani M, Ottani F, Ferrario M, Corral J, Margaglione M. Prothrombotic genetic risk factors in young survivors of myocardial infarction. Blood 1999; 94: 46-51.
    PubMedGoogle Scholar
  • 31 Boncler M, Rozalski M, Chizynski K, Watala C. Analysis of platelet glyco-proteins polymorphisms in patients with ischemic heart disease - a preliminary study in Polish population. Thromb Haemost 1999; 82 (Suppl) 377.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Moshfegh Kh, Wuillemin WA, Redondo M, Lammle B, Liechti S, Meyer BJ. Platelet polymorphisms of GPIa/IIa (Collagen) and GPIIb/IIIa (Fibrinogen) receptors and the risk of myocardial infarction. Thromb Haemost 1999; 82 (Suppl) 361.
    PubMedGoogle Scholar
  • 33 Hooper WC, Lally C, Austin H, Benson J, Dilley A, Wenger NK, Whitsett C, Rawlins P, Evatt BL. The relationship between polymorphisms in the endothelial cell nitric oxide synthase gene and the platelet GPIIIa gene with myocardial infarction and venous thromboembolism in African Americans. Chest 1999; 116: 880-6.
    CrossrefPubMedGoogle Scholar
  • 34 Bottiger C, Kastrati A, Koch W, Mehilli J, Seidl H, Schomig K, von Beckerath N, Schomig A. HPA-1 and HPA-3 polymorphisms of the platelet fibrinogen receptor and coronary artery disease and myocardial infarction. Thromb Haemost 2000; 83: 559-62.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Carter AM, Ossei-Gerning N, Grant PJ. Platelet glycoprotein IIIa PlA polymorphism in young men with myocardial infarction. Lancet 1996; 348: 485-6.
    PubMedGoogle Scholar
  • 36 Garg UC, Arnett DK, Folsom AR, Province MA, Williams RR, Eckfeldt JH. Lack of association between platelet glycoprotein IIb/IIIa receptor PlA polymorphism and coronary artery disease or carotid intima-media thickness. Thromb Res 1998; 89: 85-9.
    CrossrefPubMedGoogle Scholar
  • 37 Sperr WR, Huber K, Roden M, Janisiw M, Lang T, Graf S, Maurer G, Mayr WR, Panzer S. Inherited platelet glycoprotein polymorphisms and a risk for coronary heart disease in young central Europeans. Thromb Res 1998; 90: 117-23.
    CrossrefPubMedGoogle Scholar
  • 38 Walter DH, Schachinger V, Elsner M, Dimmeler S, Zeiher AM. Platelet glycoprotein IIIa polymorphisms and risk of coronary stent thrombosis. Lancet 1997; 350: 1217-9.
    CrossrefPubMedGoogle Scholar
  • 39 Mehilli J, Kastrati A, Koch W, Gawaz M, Elezi S, Kettling C, Schomig K, von Beckerath N. Patients Homozygous for the PIA2 allele coding for platelet glycoprotein IIIa are at increased risk for stent vessel thrombosis. Circulation 1998; 98 (Suppl I) I288.
    PubMedGoogle Scholar
  • 40 Kastrati A, Schomig A, Seyfarth M, Koch W, Elezi S, Bottiger C, Mehilli J, Schomig K, von Beckerath N. PlA polymorphism of platelet glycoprotein IIIa and risk of restenosis after coronary stent placement. Circulation 1999; 99: 1005-10.
    CrossrefPubMedGoogle Scholar
  • 41 Petitti DB. Meta-analysis, decision analysis, and cost-effectiveness analysis: methods for quantitative synthesis in medicine. New York: Oxford University Press; 1994
    Google Scholar
  • 42 Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev 1987; 9: 1-30.
    CrossrefPubMedGoogle Scholar
  • 43 Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008-12.
    CrossrefPubMedGoogle Scholar
  • 44 Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-34.
    CrossrefPubMedGoogle Scholar
  • 45 Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol 2000; 20: 484-92.
    CrossrefPubMedGoogle Scholar
  • 46 Eriksson P, Kallin B, van’t Hooft FM, Bavenholm P, Hamsten A. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci USA 1995; 92: 1851-5.
    CrossrefPubMedGoogle Scholar
  • 47 Rosendaal FR, Siscovick DS, Schwartz SM, Beverly RK, Psaty BM, Longstreth Jr WT, Raghunathan TE, Koepsell TD, Reitsma PH. Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood 1997; 89: 2817-21.
    PubMedGoogle Scholar
  • 48 Topol EJ, Califf RM, Weisman HF, Ellis SG, Tcheng JE, Worley S, Ivanohe R, George BS, Fintel D, Weston M, Sigmon K, Anderson KM, Lee KL, Willerson JT. on behalf of The EPIC investigators.. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. The EPIC Investigators. Lancet 1994; 343: 881-6.
    CrossrefPubMedGoogle Scholar
  • 49 Kuivenhoven JA, Jukema JW, Zwinderman AH, de Knijff P, McPherson R, Bruschke AV, Lie KI, Kastelein JJ. The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group. N Engl J Med 1998; 338: 86-93.
    CrossrefPubMedGoogle Scholar
  • 50 Cooke GE, Bray PF, Hamlington JD, Pham DM, Goldschmidt-Clermont PJ. PlA2 polymorphism and efficacy of aspirin. Lancet 1998; 351: 1253.
    CrossrefPubMedGoogle Scholar
  • 51 Undas A, Sanak M, Musial J, Szczeklik A. Platelet glycoprotein IIIa polymorphism, aspirin, and thrombin generation. Lancet 1999; 353: 982-3.
    CrossrefPubMedGoogle Scholar
  • 52 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. Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 1999; 19: 1142-7.
    CrossrefPubMedGoogle Scholar
  • 53 Michelson AD, Furman MI, Goldschmidt-Clermont P, Mascelli MA, Hendrix C, Coleman L, Hamlington J, Barnard MR, Kickler T, Christie DJ, Kundu S, Bray PF. Platelet GP, III a Pl(A) polymorphisms display different sensitivities to agonists. Circulation 2000; 101: 1013-8.
    CrossrefPubMedGoogle Scholar
  • 54 Goldschmidt-Clermont P, Weiss E, Shear W, Kennedy S, Kickler T, Becker L, Bray D. Platelets from PLA2 (-) individuals bind more exogenous fibrinogen than platelet from PLA2 (+) individual. Blood 1996; 88: 26a.
    PubMedGoogle Scholar
  • 55 Lasne D, Krenn M, Pingault V, Arnaud E, Fiessinger JN, Aiach M, Rendu F. Interdonor variability of platelet response to thrombin receptor activation: influence of PlA2 polymorphism. Br J Haematol 1997; 99: 801-7.
    CrossrefPubMedGoogle Scholar
  • 56 Goodall AH, Curzen N, Panesar M, Hurd C, Knight CJ, Ouwehand WH, Fox KM. Increased binding of fibrinogen to glycoprotein IIIa-proline33 (HPA-1b, PlA2, Zwb) positive platelets in patients with cardiovascular disease. Eur Heart J 1999; 20: 742-7.
    CrossrefPubMedGoogle Scholar
  • 57 Vijayan KV, Goldschmidt-Clermont PJ, Roos C, Bray PF. The Pl(A2) polymorphism of integrin beta(3) enhances outside-in signaling and adhesive functions. J Clin Invest 2000; 105: 793-802.
    CrossrefPubMedGoogle Scholar
  • 58 Bray PF. Integrin polymorphisms as risk factors for thrombosis. Thromb Haemost 1999; 82: 337-44.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 59 LeLorier J, Gregoire G, Benhaddad A, Lapierre J, Derderian F. Discrepancies between meta-analyses and subsequent large randomized, controlled trials. N Engl J Med 1997; 337: 536-42.
    CrossrefPubMedGoogle Scholar
  • 60 Blettner M, Sauerbrei W, Schlehofer B, Scheuchenpflug T, Friedenreich C. Traditional reviews, meta-analyses and pooled analyses in epidemiology. Int J. Epidemiol 1999; 28: 1-9.
    CrossrefPubMedGoogle Scholar
  • 61 McAuley L, Ba’ Pham Tugwell P, Moher D. Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses?. The Lancet 2000; 356: 1228-31.
    CrossrefPubMedGoogle Scholar