Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

J. Corral; R. González-Conejero; J. Rivera; F. Ortuño; P. Aparicio; V. Vicente

doi:10.1055/s-0037-1614605

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 81(06): 951-956
DOI: 10.1055/s-0037-1614605

Letters to the Editor

Schattauer GmbH

Role of the 807 C/T Polymorphism of the α₂ Gene in Platelet GP Ia Collagen Receptor Expression and Function

Effect in Thromboembolic Diseases

Authors

J. Corral

¹From the Unit of Onco-Hematology and Hemotherapy, Murcia, Spain, Biochemistry Department, School of Medicine, Hospital General Universitario, Murcia, Spain
R. González-Conejero

¹From the Unit of Onco-Hematology and Hemotherapy, Murcia, Spain, Biochemistry Department, School of Medicine, Hospital General Universitario, Murcia, Spain
J. Rivera

¹From the Unit of Onco-Hematology and Hemotherapy, Murcia, Spain, Biochemistry Department, School of Medicine, Hospital General Universitario, Murcia, Spain
F. Ortuño

¹From the Unit of Onco-Hematology and Hemotherapy, Murcia, Spain, Biochemistry Department, School of Medicine, Hospital General Universitario, Murcia, Spain
P. Aparicio

¹From the Unit of Onco-Hematology and Hemotherapy, Murcia, Spain, Biochemistry Department, School of Medicine, Hospital General Universitario, Murcia, Spain
V. Vicente

¹From the Unit of Onco-Hematology and Hemotherapy, Murcia, Spain, Biochemistry Department, School of Medicine, Hospital General Universitario, Murcia, Spain

Abstract

Summary

The variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

Full Text

References

References
1 Sixma JJ, van Zanten GH, Huizinga EG, Martijn van der Plas R, Verkley M, Wu YP, Gros P, de Groot PG. Platelet adhesion: an update. Thromb Haemost 1997; 78: 434-8.
2 Santoro SA, Zutter MM. The α₂β₁ integrin: a collagen receptor on platelets and other cells. Thromb Haemost 1995; 74: 813-21.
3 Zutter MM, Santoro SA. Widespread histologic distribution of the α₂β₁ integrin cell-surface collagen receptor. Am J Pathol 1990; 137: 113-20.
4 Nieuwenhuis HK, Akkerman JWN, Houdijk WPM, Sixma JJ. Human blood platelets showing no response to collagen fail to express surface glycoprotein Ia. Nature 1985; 318: 470-2.
5 Nieuwenhuis HK, Sakariasen S, Houdijk WPM, Nievelstein PFEM, Sixma JJ. Deficiency of platelet membrane glycoprotein Ia associated with a decreased platelet adhesion to subendothelium: a defect in platelet spreading. Blood 1986; 68: 692-5.
6 Kehrel B, Balleisen L, Kokott R, Mesters R, Stenzinger W, Clemetson KJ, van de Loo J. Deficiency of intact thrombospondin and membrane glycoprotein Ia in platelets with defective collagen-induced aggregation and spontaneous loss of disorder. Blood 1988; 71: 1074-8.
7 Deckmyn H, Chew SL, Vermylen L. Lack of platelet response to collagen associated with an autoantibody against glycoprotein Ia: a novel cause of acquired qualitative platelet dysfunction. Thromb Haemost 1990; 64: 74-9.
8 Deckmyn H, Zhang J, Van Houtte E, Vermylen J. Production and nucleotide sequence of an inhibitory human IgM autoantibody directed against platelet glycoprotein Ia/IIa. Blood 1994; 84: 1968-74.
9 Kunicki TJ, Orchekowski R, Annis D, Honda Y. Variability of integrin α₂β₁ activity on human platelets. Blood 1993; 82: 2693-703.
10 Kunicki TJ, Kritzik M, Annis DS, Nugent DJ. Hereditary variation in platelet integrin α₂β₁ density is associated with two neutral polymorphisms in the α₂ gene coding sequence. Blood 1997; 89: 1939-43.
11 World Health Organization Ischemic heart disease registers: report of the Fifth Work Group, including a second revision of the operating protocol, Copenhagen, Denmark, April 26-29 1971. Copenhagen, Denmark; World Health Organization, Regional Office for Europe: 1971
12 Special report from the National Institute of Neurological Disorders and Stroke Classification of Cerebrovascular Diseases III. Stroke. 1990; 21:: 637-76.
13 Mustard JF, Perry DW, Ardlie NG, Packham MA. Preparation of suspensions of washed platelets from humans. Br J Haematol 1972; 22: 123-204.
14 Sambrook J, Fritsch EF, Maniatis T.. Molecular cloning: a laboratory manual. 2nd ed. CSH Laboratory Press; Cold Spring Harbor, New York: 1989
15 Takada Y, Hemler ME. The primary structure of the VLA-2/collagen receptor alpha-2 subunit (platelet GP Ia): homology to other integrins and the presence of a possible collagen-binding domain. J Cell Biol 1989; 109: 397-407.
16 Corral J, Iniesta JA, González-Conejero R, Vicente V. Detection of Factor V Leiden from a drop of blood by PCR-SSCP. Thromb Haemost 1996; 76: 735-7.
17 Lozano ML, Rivera J, González-Conejero R, Moraleda JM, Vicente V. Loss of high affinity thrombin receptors during platelet concentrate storage impairs the reactivity of platelets to thrombin. Transfusion 1997; 37: 368-75.
18 Fraker DJ, Speck JC. Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphenylglycoluril. Biochem Biophys Res Commun 1978; 80: 849-57.
19 Rivera J, Sanchez-Roig MJ, Rosillo MC, Moraleda JM, Vicente V. Stability of glycoproteins Ib/IX and IIb/IIIa during preparation and storage of platelet concentrates: Detection by binding assays with epitope-defined monoclonal antibodies and physiological ligands. Vox Sang 1994; 67: 166-71.
20 Munson PJ, Rodbard D. LIGAND: A versatile computerized approach for characterization of ligand binding system. Anal Biochem 1980; 107: 220-39.
21 Ortuño F, Ferrer F, Lozano ML, Heras I, Moraleda JM, Vicente V. Differences in phycoerythrin- or fluorescein-isothiocyanate conjugated 8G12 on CD34+ cell evaluation. Haematologica 1997; 82: 334-5.
22 Hernández-Caselles T, Martínez-Esparza M, Lazarovitz A, Aparicio P. Specific regulation of VLA-4 and α4β7 integrin expression on human activated T lymphocytes. J Immunol 1996; 156: 3668-77.
23 Niiya K, Hodson E, Bader R, Byers-Ward V, Koziol JA, Plow EF, Ruggeri ZM. Increasing surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation. Blood 1987; 70: 475-80.
24 Pacifici R, Roman J, Kimble R, Civitelli R, Brownfield CM, Bizzarri C. Ligand binding to monocyte alpha 5 beta 1 integrin activates the alpha 2 beta 1 receptor via the alpha 5 subunit cytoplasmic domain and protein kinase C. J Immunol 1994; 153: 2222-33.
25 Hemler ME. VLA proteins in the integrin family: structures, functions, and their role in leukocytes. Ann Rev Immunol 1990; 8: 365-400.
26 Santoso SA, Kiefel V, Mueller-Erkhardt C. Platelet alloantigens Bra/Brb are expressed on the very late activation antigen 2 (VLA-2) of T-lymphocytes. Hum Immunol 1989; 225: 237-46.
27 Zutter MM, Santoro SA, Painter AS, Tsung YL, Gafford A. The human α₂ integrin gene promoter. J Biol Chem 1994; 269: 463-9.
28 Zutter MM, Painter AA, Staatz WD, Tsung YL. Regulation of α₂ integrin gene expression in cells with megakaryocytic features: a common theme of three necessary elements. Blood 1995; 86: 3006-14.
29 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.
30 Green F, Humphries S. Genetic determinants of arterial thrombosis. Bail-lière´s Clinical Haematology 1994; 7: 675-92.
31 Di Minno G, Grandone E, Margaglione M. Clinical relevance of polymorphic markers of arterial thrombosis. Thromb Haemost 1997; 78: 462-6.
32 Clarke R, Daly L, Robinson K. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991; 324: 1149-55.
33 Rosendaal FR, Siscovick DS, Schwarrtz SM, Psaty BM, Raghunathan TE, Vos HL. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 1997; 90: 1747-50.
34 Rosendaal FR, Siscovick DS, Schwarrtz SM, Beverly RK, Psaty BM, Longstreth 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.
35 Iacoviello L, Castelnuovo A, Knijff P, D"Orazio A, Amore C, Arboretti R, Kluft C, Donati MB. Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction. N Engl J Med 1998; 338: 79-85.
36 Kohler HP, Stickland MH, Ossei-Gerning N, Carter A, Mikkola H, Grant PJ. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost 1998; 79: 8-13.
37 Behague Y, Poirier O, Nicaud V, Evans A, Arvelier D, Luc G, Cambou JP, Scarabin PY, Bara L, Green F, Cambien F. Beta fibrinogen gene polymorphisms are associated with plasma fibrinogen and coronary artery disease in patients with myocardial infarction. The ECTIM study. Etude Cas-Temoins sur l’ Infarctus du Myocarde. Circulation 1996; 3: 440-9.
38 Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641-4.
39 Wenzel K, Felix S, Kleber FX, Brachold R, Menke T, Schattke S, Schulte KL, Gläser C, Rohde K, Baumann G, Speer A. E-selectin polymorphism and atherosclerosis: an association study. Hum Mol Gen 1994; 3: 1935-7.
40 Norlund L, Holm J, Zöller B, Öhlin AK. A common thrombomodulin amino acid dimorphism is associated with myocardial infarction. Thromb Haemost 1997; 77: 248-51.
41 Ireland H, Kunz G, Kyriakoulis K, Stubbs PJ, Lane DA. Thrombomodulin gene mutations associated with myocardial infarction. Circulation 1997; 96: 15-8.
42 Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler T, Becker LC, Weiss JL, Gerstenblith G, Goldschmidt-Clermont J. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 1996; 334: 1090-4.
43 Murata M, Matsubara Y, Kawano K, Zama T, Aoki N, Yoshino H, Watanabe G, Ishikawa K, Ikeda Y. Coronary artery disease and polymorphisms in a receptor mediating shear stress-dependent platelet activation. Circulation 1997; 96: 3281-6.
44 Keely PJ, Parise LV. Theα₂β₁ integrin is a necessary co-receptor for collagen-induced activation of Syk and the subsequent phosphorilation of phospolipase Cγ2 in platelets. J Biol Chem 1996; 271: 26668-76.