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Thromb Haemost 1998; 80(03): 449-456
DOI: 10.1055/s-0037-1615228
Rapid Communications
Schattauer GmbH

Analysis of Platelet Glycoprotein Ia (α2 Integrin) Allele Frequencies in Three North American Populations Reveals Genetic Association between Nucleotide 807C/T and Amino Acid 505 Glu/Lys (HPA-5) Dimorphisms

Alexander P. Reiner
1   From the Puget Sound Blood Center and Department of Medicine, University of Washington, Seattle, Washington, USA
,
Kaelen M. Aramaki
1   From the Puget Sound Blood Center and Department of Medicine, University of Washington, Seattle, Washington, USA
,
Gayle Teramura
1   From the Puget Sound Blood Center and Department of Medicine, University of Washington, Seattle, Washington, USA
,
Lakshmi Gaur
1   From the Puget Sound Blood Center and Department of Medicine, University of Washington, Seattle, Washington, USA
› Author Affiliations
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Publication History

Received 03 November 1997

Accepted after resubmission 27 May 1998

Publication Date:
08 December 2017 (online)

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Summary

Glycoprotein Ia (α2 integrin) is a subunit of the heterodimeric membrane complex (GPIa/IIa) that mediates platelet adhesion to collagen. Several nucleotide sequence variations of GPIa have been described. A nucleotide 1648 G/A dimorphism that leads to a Glu/Lys substitution at amino acid 505 is responsible for the human platelet antigen system, HPA-5. Recently, two other linked GPIa nucleotide dimorphisms involving codons Phe224 and Thr246 were identified: a C/T substitution at nucleotide 807 and a G/A substitution at nucleotide 873 (1). Using restriction enzyme digestion of amplified GPIa genomic DNA fragments (PCR-RFLP) to distinguish genotypes, we have determined the allele frequencies of the GPIa 807C/T and Glu/Lys505 dimorphisms in three North American populations, and a panel of non-human primates. Our results indicate a genetic relationship between the 807C/T and Glu/Lys505 dimorphisms that leads to an evolutionary model of GPIa isoforms.

 

  • References

  • 1 Kunicki TJ, Kritzik M, Annis DS, Nugent DJ. Hereditary variation in platelet integrin a2b1 density is associated with two silent polymorphisms in the a2 gene coding sequence. Blood 1997; 89: 1939-43.
    PubMedGoogle Scholar
  • 2 Santoro SA, Zutter MM. The a2b1 integrin: A collagen receptor on platelets and other cells. Thromb Haemost 1995; 74: 813-21.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 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.
    CrossrefPubMedGoogle Scholar
  • 4 Kehrel B, Balleisen L, Kokott R, Mesters R, Stenzinger W, Clemetson KJ, van de Loo J. Deficiency of intact thrombospondin and membrane glyco-protein Ia in platelets with defective collagen-induced aggregation and spontaneous loss of disorder. Blood 1988; 71: 1074-8.
    PubMedGoogle Scholar
  • 5 Handa M, Watanabe K, Kawai Y, Kamata T, Koyama T, Nagai H, Ikeda Y. Platelet unresponsiveness to collagen: Involvement of glycoprotein Ia-IIa (a2b1 integrin) deficiency associated with a myeloproliferative disorder. Thromb Haemost 1995; 73: 521-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Deckmyn H, Chew SL, Vermylen J. 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.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Kunicki TJ, Orchekowski R, Annis D, Honda Y. Variability of integrin a2b1 activity on human platelets. Blood 1993; 82: 2693-703.
    PubMedGoogle Scholar
  • 8 Takada Y, Hemler ME. The primary structure of the VLA-2/collagen receptor a2 subunit (platelet GPIa): Homology to other integrins and the presence of a possible collagen-binding domain. J Cell Biol 1989; 109: 397-407.
    CrossrefPubMedGoogle Scholar
  • 9 Santoso S, Kalb R, Walka M, Kiefel V, Mueller-Eckhardt C, Newman PJ. The human platelet alloantigens Bra and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit a2). J Clin Invest 1993; 92: 2427-32.
    CrossrefPubMedGoogle Scholar
  • 10 Simsek S, Gallardo D, Ribera A, von dem Borne AEGK. The human platelet alloantigens, HPA-5(a+,b–) and HPA-5(a–,b+), are associated with a Glu505/Lys505 polymorphism of glycoprotein Ia (the a2 subunit of VLA-2). Br J Haematol 1994; 86: 671-4.
    CrossrefPubMedGoogle Scholar
  • 11 Mueller-Eckhardt C, Kiefel V, Grubert A, Kroll H, Weisheit M, Schmidt S, Mueller-Eckhardt G, Santoso S. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet 1989; 1: 363-6.
    PubMedGoogle Scholar
  • 12 Kaplan C, Morel-Kopp MC, Kroll H, Kiefel V, Schlegel N, Chesnel N, Mueller-Eckhardt C. HPA-5b (Bra) neonatal alloimmune thromboytopenia: Clinical and immunological analysis of 39 cases. Br J Haematol 1991; 78: 425-9.
    CrossrefPubMedGoogle Scholar
  • 13 Bettaieb A, Fromont P, Rodet M, Godeau B, Duedari N, Bierling P. Brb, a platelet alloantigen involved in neonatal alloimmune thrombocytopenia. Vox Sang 1991; 60: 230-4.
    PubMedGoogle Scholar
  • 14 Kiefel V, Shechter Y, Atias D, Kroll H, Santoso S, Mueller-Eckhardt C. Neonatal alloimmune thrombocytopenia due to anti-Brb (HPA-5a): Report of three cases in two families. Vox Sang 1991; 60: 244-5.
    PubMedGoogle Scholar
  • 15 Christie DJ, Pulkrabek S, Putnam JL, Slatkoff ML, Pischel KD. Posttrans-fusion purpura due to an alloantibody reactive with glycoprotein Ia/IIa (anti-HPA-5b). Blood 1991; 77: 2785-9.
    PubMedGoogle Scholar
  • 16 Bierling P, Fromont P, Bettaieb A, Duedari N. Anti-Bra antibodies in the French population. Br J Haematol 1989; 73: 428-9.
    CrossrefPubMedGoogle Scholar
  • 17 Warkentin TE, Smith JW, Hayward CPM, Ali AM, Kelton JG. Thrombocytopenia caused by passive transfusion of anti-glycoprotein Ia/IIa alloanti-body (anti-HPA-5b). Blood 1992; 79: 2480-4.
    PubMedGoogle Scholar
  • 18 Bierling P, Pignon J-M, Kuentz M, Mitjavila M-T, Fromont P, Barbu V, Goossens M, Duedari N, Vainchenker W, Vernant JP. Thrombocytopenia after bone marrow transplantation caused by a recipient origin Bra allo-antibody: Presence of mixed chimerism 3 years after the graft without hematologic relapse. Blood 1994; 83: 274-9.
    PubMedGoogle Scholar
  • 19 Sharp PA. Speculations on RNA splicing. Cell 1981; 23: 643-6.
    CrossrefPubMedGoogle Scholar
  • 20 Breathnach R, Benoist C, O’Hare K, Gannon F, Chambon P. Ovalbumin gene: Evidence for a leader sequence in mRNA and DNA sequences at the exon-intron boundaries. Proc Natl Acad Sci USA 1978; 75: 4853-7.
    CrossrefPubMedGoogle Scholar
  • 21 Mount SM. A catalogue of splice junction sequences. Nucleic Acids Res 1982; 10: 459-70.
    CrossrefPubMedGoogle Scholar
  • 22 Kalb R, Santoso S, Unkelbach K, Kiefel V, Mueller-Eckhardt C. Localization of the Br polymorphism on a 144 bp exon of the GPIa gene and its application in platelet DNA typing. Thromb Haemost 1994; 71: 651-4.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Kritzik M, Tarantino MD, Nugent DJ, Santoso S, Kunicki TJ. Nucleotide polymorphisms in the a2 gene define multiple alleles which are associated with differences in platelet α2β1 . Blood 1997; 90 (suppl): 27a.
    PubMedGoogle Scholar
  • 24 Kim HO, Jin Y, Kickler TS, Blakemore K, Kwon OH, Bray PF. Gene frequencies of the five major human platelet antigens in African American, white, and Korean populations. Transfusion 1995; 35: 863-7.
    PubMedGoogle Scholar
  • 25 Mercier P, Chicheportiche C, Dabanian C, Gamerre M, Reviron D. Platelet antigen HPA-5b (Bra) in an Algerian population. Tissue Antigens 1994; 43: 58-9.
    CrossrefPubMedGoogle Scholar
  • 26 Unkelbach K, Kalb R, Santoso S, Kroll H, Mueller-Eckhardt C, Kiefel V. Genomic RFLP typing of human platelet alloantigens Zw(PlA), Ko, Bak and Br (HPA-1, 2, 3, 5). Br J Haematol 1995; 89: 169-76.
    CrossrefPubMedGoogle Scholar
  • 27 Holensteiner A, Walchshofer S, Adler A, Kittl E-M, Mayr WR, Panzer S. Human platelet antigen gene frequencies in the Austrian population. Haemostasis 1995; 25: 133-6.
    PubMedGoogle Scholar
  • 28 Kiefel V, Santoso S, Katzmann B, Mueller-Eckhardt C. The Bra/Brb alloantigen system on human platelets. Blood 1989; 73: 2219-23.
    PubMedGoogle Scholar
  • 29 Simsek S, Faber NM, Bleeker PM, Vlekke ABJ, Huiskes E, Goldschmeding R, von dem Borne. AEGKr. Determination of human platelet antigen frequencies in the Dutch population by immunophenotyping and DNA (allele-specific restriction enzyme) analysis. Blood 1993; 81: 835-40.
    PubMedGoogle Scholar
  • 30 Chen D-F, Pastucka LT, Chen H-Y, Kadar JG, Stangel W. Simultaneous genotyping of human platelet antigens by hot start sequence-specific polymerase chain reaction with DNA polymerase AmpliTaq Gold. Vox Sang 1997; 72: 192-6.
    CrossrefPubMedGoogle Scholar
  • 31 Smith JW. Platelet specific alloantigens on the platelet glycoprotein Ia/IIa complex. Br J Haematol 1989; 72: 534-8.
    CrossrefPubMedGoogle Scholar
  • 32 Legler TJ, Köhler M, Mayr WR, Panzer S, Ohto H, Fischer GF. Geno-typing of the human platelet antigen systems 1 through 5 by multiplex polymerase chain reaction and ligation-based typing. Transfusion 1996; 36: 426-31.
    CrossrefPubMedGoogle Scholar
  • 33 Kekomäki S, Partanen J, Kekomäki R. Platelet alloantigens HPA-1, -2, -3, -5 and -6b in Finns. Transfus Med 1995; 5: 193-8.
    CrossrefPubMedGoogle Scholar
  • 34 Inostroza J, Kiefel V, Mueller-Eckhardt C. Frequency of platelet-specific antigens PlA1, Baka, Yuka, Yukb, and Bra in South American (Mapuches) Indians. Transfusion 1988; 28: 586-7.
    CrossrefPubMedGoogle Scholar
  • 35 Fujiwara K, Isa K, Oka T, Maekawajiri S, Yamane A, Akaza T, Tadokoro K, Juji T, Shibata Y, Tokunaga K. Large-scale DNA typing for human platelet alloantigens by PCR-PHFA (preferential homoduplex formation assay). Br J Haematol 1996; 95: 198-203.
    CrossrefPubMedGoogle Scholar
  • 36 Santoso S, Santoso S, Kiefel V, Masri R, Mueller-Eckhardt C. Frequency of platelet-specific antigens among Indonesians. Transfusion 1993; 33: 739-41.
    PubMedGoogle Scholar
  • 37 Urwijitaroon Y, Barusrux S, Romphruk A, Puapairoj C. Frequency of human platelet antigens among blood donors in northeastern Thailand. Transfusion 1995; 35: 868-70.
    PubMedGoogle Scholar
  • 38 Cavalli-Sforza LL, Piazza A, Menozzi P, Mountain J. Reconstruction of human evolution: Bringing together genetic, archaeological, and linguistic data. Proc Natl Acad Sci USA 1988; 85: 6002-6.
    CrossrefPubMedGoogle Scholar
  • 39 Kamata T, Puzon W, Takada Y. Identification of putative ligand binding sites within I domain of integrin α2β1 (VLA-2, CD49b/CD29). J Biol Chem 1994; 269: 9659-63.
    PubMedGoogle Scholar
  • 40 Edelman JM, Chan BM, Uniyal S, Onodera H, Wang DZ St, John NF, Damjanovich L, Latzer DB, Finberg RW, Bergelson JM. The mouse VLA-2 homologue supports collagen and laminin adhesion but not virus binding. Cell Adhes Commun 1994; 2: 131-43.
    CrossrefPubMedGoogle Scholar
  • 41 Goodman Morris. Protein Sequences in Phylogeny. In: Ayala FJ. ed. Molecular Evolution. Sunderland, Massachusetts: Sinauer Associates; 1976: 141-59.
    Google Scholar
  • 42 Reiner AP, Teramura G. A modified PCR-RFLP genotyping method demonstrates the presence of the HPA-4b platelet alloantigen in a North American Indian population. Immunohematology 1997; 13: 37-43.
    PubMedGoogle Scholar
  • 43 Dickeson SK, Walsh JJ, Santoro SA. Contributions of the I and EF hand domains to the divalent cation-dependent collagen binding activity of the a2b1 integrin. J Biol Chem 1997; 272: 7661-8.
    CrossrefPubMedGoogle Scholar
  • 44 Zutter MM. The human a2 integrin gene promoter: Identification of positive and negative regulatory elements important for cell-type and developmentally restricted gene expression. J Biol Chem 1994; 269: 463-9.
    PubMedGoogle Scholar
  • 45 Zutter MM, Painter AA, Staatz WD, Tsung YL. Regulation of a2 integrin gene expression in cells with megakaryocytic features: A common theme of three necessary elements. Blood 1995; 86: 3006-14.
    PubMedGoogle Scholar
  • 46 Matsuo K, Reid DM. Allele-specific restriction analysis of human platelet antigen system 4. Transfusion 1996; 36: 809-12.
    PubMedGoogle Scholar
  • 47 Tanaka S, Taniue A, Nagao N, Tomita T, Ohnoki S, Shibata H, Okubo Y, Yamaguchi H, Shibata Y. Genotype frequencies of the human platelet antigen, Ca/Tu, in Japanese, determined by a PCR-RFLP method. Vox Sang 1996; 70: 40-4.
    CrossrefPubMedGoogle Scholar