PDF herunterladen
Thromb Haemost 2000; 83(01): 23-28
DOI: 10.1055/s-0037-1613751
Commentary
Schattauer GmbH

A Common Polymorphism Flanking the ATG Initiator Codon of GPIbα Does not Affect Expression and Is not a Major Risk Factor for Arterial Thrombosis

J. Corral
1   From the Unit of Oncohematology and Hemotherapy, Murcia, Spain
,
M. L. Lozano
1   From the Unit of Oncohematology and Hemotherapy, Murcia, Spain
,
R. González-Conejero
1   From the Unit of Oncohematology and Hemotherapy, Murcia, Spain
,
C. Martínez
1   From the Unit of Oncohematology and Hemotherapy, Murcia, Spain
,
J. A. Iniesta
2   Neurology Department, School of Medicine, University General Hospital, Murcia, Spain
,
J. Rivera
1   From the Unit of Oncohematology and Hemotherapy, Murcia, Spain
,
V. Vicente
1   From the Unit of Oncohematology and Hemotherapy, Murcia, Spain
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 20. Mai 1999

Accepted after resubmission 23. August 1999

Publikationsdatum:
06. Dezember 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Summary

The platelet membrane glycoprotein (GP) Ibα plays a key role in the initial formation of thrombi. Polymorphisms (VNTR and HPA-2) in this receptor are associated with increased risk of coronary heart disease (CHD) and cerebral vascular disease (CVD). We investigated whether a recently described polymorphism (S/R), due to a single base change (T → C) five nucleotides upstream the initiator codon of GPIbα, might influence the expression of the protein, and be implicated in the development of arterial thrombosis.

One hundred and thirty nine healthy individuals provided blood samples for DNA analysis of platelet GPIbα polymorphisms, and for flow cytometric analysis of the surface expression of the receptor. A group of 20 S/R normal individuals and an identical number of S/S participants, age and sex matched, was investigated for the analysis of the density of various platelet receptors. The distribution of the S/R polymorphism was also analyzed in two case/control studies including 104 CVD patients, 101 CHD patients, and one control age, sex, and environmental risk factors matched for each case patient. Surface density of GPIbα showed no wide variations between individuals, was not influenced by the presence of S or R alleles, nor associated with the VNTR or HPA-2 polymorphisms. The prevalence of the S/R genotype among CVD and CHD patients was not distinct from that in the control groups. We conclude that the S/R polymorphism of GPIbα, flanking the initiator codon of the receptor, does not seem to be associated with surface levels of the protein, and is not an independent risk factor for arterial thrombosis.

Keywords

GPIbα - polymorphism - risk factor - arterial thrombosis - platelet
 

  • References

  • 1 Vicente V, Houghten RA, Ruggeri ZM. Identification of α site in the a chain of platelet glycoprotein Ib that participates in von Willebrand factor binding. J Biol Chem 1990; 265: 274-80.
    PubMedSuche in Google Scholar
  • 2 De Marco L, Mazzucato M, Masotti A, Ruggeri ZM. Localization and characterization of an α-thrombin-binding-site on platelet glycoprotein Ibα. J Biol Chem 1994; 269: 6478-84.
    PubMedSuche in Google Scholar
  • 3 Li CQ, Dong JF, Lanza F, Sanan DA, Sae-Tung G, López JA. Expression of platelet glycoprotein (GP) V in heterologous cells and evidence for its association with GP Ibα in forming a GP Ib-IX-V complex on the cell surface. J Biol Chem 1995; 270: 16302-7.
    CrossrefPubMedSuche in Google Scholar
  • 4 Wenger RH, Wicki AN, Kieffer N, Adolph S, Hameister H, Clemetson KJ. The 5´flanking region and chromosomal localization of the gene encoding human platelet membrane glycoprotein Ibα. Gene 1989; 85: 517-24.
    CrossrefPubMedSuche in Google Scholar
  • 5 Hashimoto Y, Ware J. Identification of essential GATA and Ets binding motifs within the promoter of the platelet glycoprotein Iba gene. J Biol Chem 1995; 270: 24532-9.
    CrossrefPubMedSuche in Google Scholar
  • 6 Krause DS, Perkins AS. Gotta find GATA a friend. Nat Med 1997; 03: 960-1.
    CrossrefPubMedSuche in Google Scholar
  • 7 Corral J, González-Conejero R, Lozano ML, Rivera J, Vicente V. New alleles of the platelet glycoprotein Ibα gene. Br J Haematol 1998; 103: 997-1003.
    CrossrefPubMedSuche in Google Scholar
  • 8 López JA, Ludwig EH, McCarthy BJ. Polymorphism of human glycoprotein Ibα results from a variable number of tandem repeats of a 13-amino acid sequence in the mucin-like macroglycopeptide region. J Biol Chem 1992; 267: 10055-61.
    PubMedSuche in Google Scholar
  • 9 Kaski S, Kekomäki R, Partanen J. Systematic screening for genetic polymorphism in human platelet glycoprotein Ibalpha . Immunogenetics 1996; 44: 170-6.
    CrossrefPubMedSuche in Google Scholar
  • 10 Suzuki K, Hayashi T, Akiba J, Yahagi A, Tajima K, Satoh S, Sasaki H. Sty I polymorphism at nucleotide 1610 in the human platelet glycoprotein Ib alpha gene. Jpn J Human Genet 1996; 41: 419-21.
    CrossrefPubMedSuche in Google Scholar
  • 11 Kozak M. An analysis of 5´-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res 1987; 15: 8125-48.
    CrossrefPubMedSuche in Google Scholar
  • 12 Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 1986; 44: 283-92.
    CrossrefPubMedSuche in Google Scholar
  • 13 Afshar-Kharghan V, Li CQ, Khoshnevis-Asl M, López JA. Kozak sequence polymorphism of the glycoprotein (GP) Ibα gene is a major determinant of the plasma membrane levels of the platelet GP Ib-IX-V complex. Blood 1999; 94: 186-91.
    PubMedSuche in Google Scholar
  • 14 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.
    CrossrefPubMedSuche in Google Scholar
  • 15 González-Conejero R, Lozano ML, Rivera J, Corral J, Iniesta JA, Moraleda JM, Vicente V. Polymorphisms of platelet membrane glycoprotein Ibα associated with arterial thrombotic disease. Blood 1998; 92: 2771-6.
    PubMedSuche in Google Scholar
  • 16 Kroll MH, Hellums JD, McIntire LV, Schafer AI, Moake JL. Platelets and shear stress. Blood 1996; 88: 1525-41.
    PubMedSuche in Google Scholar
  • 17 Moshfegh K, Wuillemin WA, Redondo M, Lämmle B, Beer JH, Liechti-Gallati S, Meyer BJ. Association of two silent polymorphisms of platelet glycoprotein Ia/IIa receptor with risk of myocardial infarction: a casecontrol study. Lancet 1999; 353: 351-4.
    CrossrefPubMedSuche in Google Scholar
  • 18 Afshar-Kharghan V, Khoshnevis-Asi M, Hopkins P, López JA. Polymorphism of the platelet glycoprotein (GP) Ibα Kozak sequence determines the surface level of the GP Ib-IX-V complex and risk for early myocardial infarction. Blood 1998; 92 (Suppl. 01) 2887a.
    PubMedSuche in Google Scholar
  • 19 Special Report From the National Institute of Neurological Disorders and Stroke: Classification of Cerebrovascular Diseases III. Stroke. 1990; 21: 637-76.
    PubMedSuche in Google Scholar
  • 20 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
    Suche in Google Scholar
  • 21 Wenger RH, Kieffer N, Wicki AN, Clemetson KJ. Structure of human blood platelet membrane glycoprotein Ibα gene. Biochem Biophys Res Commun 1988; 156: 389-95.
    CrossrefPubMedSuche in Google Scholar
  • 22 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.
    PubMedSuche in Google Scholar
  • 23 Handa M, Titani K, Holland LZ, Roberts JR, Ruggeri ZM. The von Willebrand factor-binding domain of platelet membrane glycoprotein Ib. Characterization by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragments. J Biol Chem 1986; 261: 12579-85.
    PubMedSuche in Google Scholar
  • 24 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.
    CrossrefPubMedSuche in Google Scholar
  • 25 Fraker DJ, Speck JC. Protein and cell membrane iodinations with a sparinglysoluble-chloroamide,1,3,4,6-tetrachloro-3a,6a-diphenylglycoluril. Biochem Biophys Res Commun 1978; 80: 849-57.
    CrossrefPubMedSuche in Google Scholar
  • 26 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.
    PubMedSuche in Google Scholar
  • 27 Munson PJ, Rodbard D. LIGAND: A versatile computerized approach for characterization of ligand binding system. Anal Biochem 1980; 107: 220-39.
    CrossrefPubMedSuche in Google Scholar
  • 28 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.
    PubMedSuche in Google Scholar
  • 29 Corral J, González-Conejero R, Rivera J, Ortuño F, Aparicio P, Vicente V. Role of the 807 C/T polymorphism of the α2 gene in the platelet GP Ia collagen receptor expression and function: effect in thromboembolic diseases. Transfusion 1999; 39: 372-8.
    CrossrefPubMedSuche in Google Scholar
  • 30 Kanaji T, Okamura T, Osaki K, Kuroiwa M, Shimoda K, Hamasaki N, Niho Y. A common genetic polymorphism (46 C to T substitution) in the 5´-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level. Blood 1998; 91: 2010-4.
    PubMedSuche in Google Scholar
  • 31 Kohler HP, Futers TS, Grant PJ. FXII (46C→T) polymorphism and in vivo generation of FXII activity. Thromb Haemost 1999; 81: 745-7.
    Thieme ConnectPubMedSuche in Google Scholar
  • 32 Nurden P. Bidirectional trafficking of membrane glycoproteins following platelet activation in suspension. Thromb Haemost 1997; 78: 1305-15.
    Thieme ConnectPubMedSuche in Google Scholar
  • 33 Mazzucato M, Pradelles P, de Angelis V, Steffen A, de Marco L. Frequency and functional relevance of genetic threonine145/methionine145 dimorphism in platelet glycoprotein Ibα in Italian population. Transfusion 1996; 36: 891-4.
    CrossrefPubMedSuche in Google Scholar
  • 34 van Zanten GH, Heijnen HF, Win Y, Schut-Hese KM, Slootweg PJ, de Groot PG, Sixma JJ, Nieuwland R. A fifty percent reduction of platelet surface glycoprotein Ib does not affect platelet adhesion under flow conditions. Blood 1998; 91: 2353-9.
    PubMedSuche in Google Scholar
  • 35 López JA. The platelet glycoprotein Ib-IX complex. Blood Coag Fibrinol 1994; 05: 97-119.
    CrossrefPubMedSuche in Google Scholar
  • 36 Nurden AT. Polymorphisms of human platelet membrane glycoproteins: Structure and clinical significance. Thromb Haemost 1995; 74: 345-51.
    Thieme ConnectPubMedSuche in Google Scholar