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Thromb Haemost 2001; 86(06): 1360-1362
DOI: 10.1055/s-0037-1616735
Review Article
Schattauer GmbH

Prevalence of a 23bp Insertion in Exon 3 of the Endothelial Cell Protein C Receptor Gene in Venous Thrombophilia

Mario von Depka
1   Department of Haematology/Oncology, Hannover Medical School
,
Andreas Czwalinna
1   Department of Haematology/Oncology, Hannover Medical School
,
Roswith Eisert
1   Department of Haematology/Oncology, Hannover Medical School
,
Cornelia Wermes
1   Department of Haematology/Oncology, Hannover Medical School
,
Inge Scharrer
2   Centre of Internal Medicine I, University Hospital Frankfurt, Germany
,
Arnold Ganser
1   Department of Haematology/Oncology, Hannover Medical School
,
Silke Ehrenforth
2   Centre of Internal Medicine I, University Hospital Frankfurt, Germany
› Author Affiliations
Further Information

Publication History

Received 21 August 2001

Accepted after resubmission 06 August 2001

Publication Date:
12 December 2017 (online)

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Summary

Background: The endothelial cell protein C receptor (EPCR) enhances protein C activation by the thrombin-thrombomodulin complex. As evidence is accumulating that EPCR is an important component of the protein C anticoagulant pathway, polymorphisms in the EPCR gene might be candidate risk factors predisposing to venous thromboembolism (VTE). Recently, a 23bp insertion in exon 3 of the EPCR gene has been identified, which duplicates the preceding 23 bases and results in a STOP codon downstream from the insertion point. However, the clinical significance of this mutation in VTE remains to be clarified. Methods and Results: In this study we evaluated the EPCR 23bp insertion in 889 patients with documented VTE and in 500 healthy controls. The prevalence of the EPCR insertion among patients was 0.1%, which was not significantly different compared to controls (0.6%, p = 0.1). Conclusions: Our findings showed that the EPCR 23bp insertion is very rare in both patients with VTE and the general population and failed to support an association between the EPCR 23bp insertion and an increased risk of VTE.

Keywords

EPCR - venous thromboembolism - protein C pathway - genetics
 

  • References

  • 1 Bangalore N, Drohan WN, Orthner CL. High affinity binding sites for activated protein C and protein C on cultured human umbilical vein endothelial cells independent of protein S and distinct from known ligands. Thromb Haemost 1994; 72: 465.
    Thieme ConnectPubMedSearch in Google Scholar
  • 2 Fukudome K, Esmon CT. Identification, cloning and regulation of a novel endothelial cell protein C/activated protein C receptor: cell surface expression and direct ligand binding by the soluble receptor. J Biol Chem 1994; 271: 17491.
    PubMedSearch in Google Scholar
  • 3 Laszik Z, Mitro A, Taylor Jr FB, Ferrell G, Esmon CT. Human protein C receptor is present primarily on endothelium of large blood vessels: implications for the control of the protein C pathway. Circulation 1997; 96: 3633.
    CrossrefPubMedSearch in Google Scholar
  • 4 Fukudome K, Ye X, Tsuneyoshi N, Tokunaga O, Sugawara K, Mizokami H, Kimoto M. Activation mechanism of anticoagulant protein C in large blood vessels involving the endothelial cell protein C receptor. J Exp Med 1998; 187: 1029.
    CrossrefPubMedSearch in Google Scholar
  • 5 Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci USA 1996; 93: 10212.
    CrossrefPubMedSearch in Google Scholar
  • 6 Xu J, Qu DF, Esmon LN, Esmon CT. Metalloproteolytic release of endothelial cell protein C receptor. J Biol Chem 2000; 275: 6038-44.
    CrossrefPubMedSearch in Google Scholar
  • 7 Regan LM, Stearns-Kurosawa DJ, Kurosawa S, Mollica J, Fukudome K, Esmon CT. The endothelial cell protein C receptor. Inhibition of activated protein C anticoagulant function without modulation of reaction with proteinase inhibitors. J Biol Chem 1996; 271: 17499.
    CrossrefPubMedSearch in Google Scholar
  • 8 Liaw PCY, Neuenschwander PF, Smirnov MD, Esmon CT. Mechanisms by which soluble endothelial cell protein C receptor modulates protein C and activated protein C function. J Biol Chem 2000; 275: 5447-52.
    CrossrefPubMedSearch in Google Scholar
  • 9 Esmon CT. The endothelial cell protein C receptor. Thromb Haemost 2000; 83: 639.
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Simmonds RE, Lane DA. Structural and functional implications of the intron/exon organization of the human endothelial cell protein C/activated protein C receptor (EPCR) gene: comparison with the structure of CD1/ major histocompatibility complex a1 and a2 domains. Blood 1999; 94: 632-41.
    CrossrefPubMedSearch in Google Scholar
  • 11 Merati G, Biguzzi E, Oganesyan R, Fetiveau R, Qu D, Buciarelli P, Stearns-Kurosawa DJ, Mannucci PM, Esmon CT, Faioni EM. A 23bp insertion in the endothelial protein C receptor (EPCR) gene in patients with myocardial infarction and deep vein thrombosis [abstract]. Thromb Haemost Suppl: 1999; 507.
    PubMedSearch in Google Scholar
  • 12 von Depka M, Nowak-Göttl U, Eisert R, Dieterich C, Barthels M, Scharrer I, Ganser A, Ehrenforth S. Increased lipoprotein(a) levels as an independent risk factor for venous thromboembolism. Blood 2000; 96: 3364-8.
    PubMedSearch in Google Scholar
  • 13 Xu J, Esmon NL, Esmon CT. Reconstitution of the human endothelial cell protein C receptor with thrombomodulin in phosphatidylcholine vesicles enhances protein C activation. J Biol Chem 1999; 274: 6704-10.
    CrossrefPubMedSearch in Google Scholar
  • 14 Taylor Jr FB, Peer GT, Lockhart MS, Ferrell G, Esmon CT. Endothelial cell protein C receptor plays an important role in protein C activation in vivo. Blood, 2001; 97: 1685-8.
    CrossrefPubMedSearch in Google Scholar
  • 15 Van de Water NS, French JK, McDowell J, Browett PJ. The Endothelial Protein C Receptor (EPCR) 23bp Insert in Patients with Myocardial Infarction. Thromb Haemost 2001; 85: 749-51.
    Thieme ConnectPubMedSearch in Google Scholar