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

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.

Keywords

Platelet glycoprotein - myocardial infarction - melting curve analysis - genetics - ethnic difference

• 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.