Thromb Haemost 2001; 85(02): 226-230
DOI: 10.1055/s-0037-1615702
Review Article
Schattauer GmbH

Lack of Association between the Platelet Glycoprotein Ia C807T Gene Polymorphism and Myocardial Infarction in Japanese

An Approach Entailing Melting Curve Analysis with Specific Fluorescent Hybridization Probes
Hiroyuki Morita
1   Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
,
Hiroki Kurihara
1   Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
,
Yasushi Imai
1   Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
,
Takao Sugiyama
2   The Institute for Adult Diseases Asahi Life Foundation, University of Tokyo, Tokyo, Japan
,
Chikuma Hamada
3   Department of Pharmacoepidemiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
,
Eiichi Sakai
4   Nihon Gene Research Laboratories Inc, Sendai, Japan
,
Mitsuko Mori
4   Nihon Gene Research Laboratories Inc, Sendai, Japan
,
Ryozo Nagai
1   Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

Received 18 February 2000

Accepted after resubmission 30 August 2000

Publication Date:
08 December 2017 (online)

Summary

The platelet-collagen receptor, glycoprotein Ia/IIa (integrin α2β1) plays a fundamental role in the adhesion of platelets to fibrillar collagen, an event leading to platelet activation and thrombus formation and contributing to the pathogenesis of thrombotic disease. Further, glyco-protein Ia/IIa receptor density and function may be associated with two linked and silent polymorphisms (807C/T and 873G/A) within the glyco-protein Ia gene. We tested the extent to which these polymorphisms serve as genetic markers of myocardial infarction in a Japanese population. A case-control study was carried out using 210 Japanese myocar-dial infarction patients and 420 age- and sex-matched controls. Geno-typing was accomplished using PCR followed by melting curve analysis with specific fluorescent hybridization probes. The 807CC, CT, TT genotypes linked perfectly to the 873GG, GA, AA genotypes, respectively. Allele frequencies of the 807T (873A) variant were similar in the control and patient groups (0.373 vs. 0.352). The 807T and 873A variants of platelet glycoprotein Ia gene are common and in a perfect linkage in the Japanese population, but it appears unlikely that the 807T (873A) variant represents a useful marker of increased risk for myocardial infarction.

 
  • References

  • 1 Stein B, Fuster V. Antithrombotic therapy in acute myocardial infarction: prevention of venous, left ventricular and coronary artery thromboembolism. Am J Cardiol 1989; 64: 33B-40B.
  • 2 Nieuwenhuis HK, Akkerman JW, Houdijk WP, Sixma JJ. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature 1985; 318: 470-2.
  • 3 Santoro SA. Identification of a 160,000 dalton platelet membrane protein that mediates the initial divalent cation-dependent adhesion of platelets to collagen. Cell 1986; 46: 913-20.
  • 4 Hynes RO. Integrins: a family of cell surface receptors. Cell 1987; 48: 549-54.
  • 5 Kunicki TJ, Nugent DJ, Staats SJ, Orchekowski RP, Wayner EA, Carter WG. The human fibroblast class II extracellular matrix receptor mediates platelet adhesion to collagen and is identical to the platelet glycoprotein Ia-IIa complex. J Biol Chem 1988; 263: 4516-9.
  • 6 Staatz WD, Rajpara SM, Wayner EA, Carter WG, Santoro SA. The membrane glycoprotein Ia-IIa (VLA-2) complex mediates the Mg++-dependent adhesion of platelets to collagen. J Cell Biol 1989; 108: 1917-24.
  • 7 Coller BS, Beer JH, Scudder LE, Steinberg MH. Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GPIa/IIa and an indirect interaction with platelet GPIIb/IIIa mediated by adhesive proteins. Blood 1989; 74: 182-92.
  • 8 Saelman EU, Nieuwenhuis HK, Hese KM, de Groot PG, Heijnen HF, Sage EH, Williams S, McKeown L, Gralnick HR, Sixma JJ. Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (α2β1-integrin). Blood 1994; 83: 1244-50.
  • 9 Kirchhofer D, Tschopp TB, Steiner B, Baumgartner HR. Role of collagen-adherent platelets in mediating fibrin formation in flowing whole blood. Blood 1995; 86: 3815-22.
  • 10 Kunicki TJ, Orchekowski R, Annis D, Honda Y. Variability of integrin α2β1 activity on human platelets. Blood 1993; 82: 2693-703.
  • 11 Kunicki TJ, Kritzik M, Annis DS, Nugent DJ. Hereditary variation in platelet integrin α2β1 density is associated with two silent polymorphisms in the α2 gene coding sequence. Blood 1997; 89: 1939-43.
  • 12 Moshfegh K, Wuillemin WA, Redondo M, Lammle B, Beer JH, LiechtiGallati S, Meyer BJ. Association of two silent polymorphisms of platelet glycoprotein Ia/IIa receptor with risk of myocardial infarction: a case-control study. Lancet 1999; 353: 351-4.
  • 13 Santoso S, Kunicki TJ, Kroll H, Haberbosch W, Gardemann A. Association of the platelet glycoprotein Ia C807T gene polymorphism with non-fatal myocardial infarction in younger patients. Blood 1999; 93: 2449-53.
  • 14 Carlsson LE, Santoso S, Spitzer C, Kessler C, Greinacher A. The α2 gene coding sequence T807/A873 of the platelet collagen receptor integrin α2β1 might be a genetic risk factor for the development of stroke in younger patients. Blood 1999; 93: 3583-6.
  • 15 SAS Institute, Inc.. SAS/STAT User’s Guide. Version 6, 4th ed. Vol 2. SAS Institute Inc; 1990
  • 16 Plow EF, Ginsberg MH. Cellular adhesion: GPIIb-IIIa as a prototypic adhesion receptor. Prog Hemost Thromb 1989; 9: 117-56.
  • 17 Coller BS. Platelets and thrombolytic therapy. N Engl J Med 1990; 322: 33-42.
  • 18 Jang Y, Lincoff AM, Plow EF, Topol EJ. Cell adhesion molecules in coronary artery disease. J Am Coll Cardiol 1994; 24: 1591-601.
  • 19 Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction.. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. N Engl J Med 1998; 338: 1488-97.
  • 20 Kritzik M, Savage B, Nugent DJ, Santoso S, Ruggeri ZM, Kunicki TJ. Nucleotide polymorphisms in the α2 gene define multiple alleles that are associated with differences in platelet α2β1 density. Blood 1998; 92: 2382-8.
  • 21 Kroll MH, Hellums JD, McIntire LV, Schafer AI, Moake JL. Platelets and shear stress. Blood 1996; 88: 1525-41.
  • 22 Bernard PS, Ajioka RS, Kushner JP, Wittwer CT. Homogeneous multiplex genotyping of hemochromatosis mutations with fluorescent hybridization probes. Am J Pathol 1998; 153: 1055-61.
  • 23 Nauck M, Wieland H, Marz W. Rapid, homogeneous genotyping of the 4G/5G polymorphism in the promoter region of the PAII gene by fluorescence resonance energy transfer and probe melting curves. Clin Chem 1999; 45: 1141-7.
  • 24 Nauck MS, Gierens H, Nauck MA, Marz W, Wieland H. Rapid genotyping of human platelet antigen 1 (HPA-1) with fluorophore-labelled hybridization probes on the LightCycler. Br J Haematol 1999; 105: 803-10.
  • 25 von Ahsen N, Schutz E, Armstrong VW, Oellerich M. Rapid detection of prothrombotic mutations of prothrombin (G20210A), factor V (G1691A), and methylenetetrahydrofolate reductase (C677T) by real-time fluorescence PCR with the LightCycler. Clin Chem 1999; 45: 694-6.
  • 26 Aslanidis C, Schmitz G. High-speed apolipoprotein E genotyping and apolipoprotein B3500 mutation detection using real-time fluorescence PCR and melting curves. Clin Chem 1999; 45: 1094-7.