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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1311-1318. Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-07-2520. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2520v1 103/4/1311    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Saposnik, B. Articles by Gandrille, S. Search for Related Content PubMed PubMed Citation Articles by Saposnik, B. Articles by Gandrille, S. Related Collections Immunotherapy Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis Beatrice Saposnik, Jean-Luc Reny, Pascale Gaussem, Joseph Emmerich, Martine Aiach, and Sophie Gandrille From the Institut National de la Santé et de la Recherche Médicale (INSERM) U 428, Paris, France; Service d'Hématologie Biologique A; Service de Médecine Vasculaire-hypertension, Hôpital Européen Georges Pompidou, Paris France; and Laboratoire d'Hémostase, Université Paris V, Paris, France. The endothelial cell protein C (PC) receptor (EPCR) facilitates PC activation by the thrombin-thrombomodulin complex. A soluble form of this receptor (sEPCR) found in plasma inhibits both activated PC (aPC) activity and PC activation by competing for PC with membrane-associated EPCR. Elevated sEPCR levels are found in approximately 20% of healthy subjects, but the mechanisms underlying this interindividual variability are unknown. We measured sEPCR levels in 100 healthy male volunteers, and observed 2 phenotypic groups of subjects. The temporal stability of sEPCR levels suggested genetic control. Extensive analysis of the EPCR gene in these subjects revealed 13 polymorphisms in complete linkage disequilibrium; these defined 3 haplotypes, 1 of which (A3) was strongly associated with high sEPCR levels. The high constitutive sEPCR levels observed in A3 haplotype carriers might reduce the efficiency of the PC system and predispose these subjects to venous thrombosis. By studying 338 patients with venous thrombosis and 338 age- and sex-matched healthy subjects, we found that the A3 haplotype was overrepresented in the patients. In multivariate analysis, subjects carrying the A3 haplotype had an increased risk of thrombosis (odds ratio [OR] = 1.8; P = .004). Thus, the A3 haplotype, which is associated with elevated plasma sEPCR levels, is a candidate risk factor for venous thrombosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Thrombosis down to the vessel wall Frits R. Rosendaal Blood 2004 103: 1179-1180. [Full Text] [PDF] This article has been cited by other articles: S. Gandrille Endothelial cell protein C receptor and the risk of venous thrombosis Haematologica, June 1, 2008; 93(6): 812 - 816. [Full Text] [PDF] S. Navarro, P. Medina, Y. Mira, A. Estelles, P. Villa, F. Ferrando, A. Vaya, R. M. Bertina, and F. Espana Haplotypes of the EPCR gene, prothrombin levels, and the risk of venous thrombosis in carriers of the prothrombin G20210A mutation Haematologica, June 1, 2008; 93(6): 885 - 891. [Abstract] [Full Text] [PDF] E. Molina, J. Hermida, J. Lopez-Sagaseta, C. Puy, and R. Montes The functional properties of a truncated form of endothelial cell protein C receptor generated by alternative splicing Haematologica, June 1, 2008; 93(6): 878 - 884. [Abstract] [Full Text] [PDF] M. Geiger Soluble protein C receptor: why? Blood, April 1, 2008; 111(7): 3301 - 3302. [Full Text] [PDF] B. Saposnik, E. Lesteven, A. Lokajczyk, C. T. Esmon, M. Aiach, and S. Gandrille Alternative mRNA is favored by the A3 haplotype of the EPCR gene PROCR and generates a novel soluble form of EPCR in plasma Blood, April 1, 2008; 111(7): 3442 - 3451. [Abstract] [Full Text] [PDF] D. Borgel, C. Bornstain, P. H. Reitsma, N. Lerolle, S. Gandrille, F. Dali-Ali, C. T. Esmon, J.-Y. Fagon, M. Aiach, and J.-L. Diehl A Comparative Study of the Protein C Pathway in Septic and Nonseptic Patients with Organ Failure Am. J. Respir. Crit. Care Med., November 1, 2007; 176(9): 878 - 885. [Abstract] [Full Text] [PDF] M. Canault, A. S. Leroyer, F. Peiretti, G. Leseche, A. Tedgui, B. Bonardo, M.-C. Alessi, C. M. Boulanger, and G. Nalbone Microparticles of Human Atherosclerotic Plaques Enhance the Shedding of the Tumor Necrosis Factor-{alpha} Converting Enzyme/ADAM17 Substrates, Tumor Necrosis Factor and Tumor Necrosis Factor Receptor-1 Am. J. Pathol., November 1, 2007; 171(5): 1713 - 1723. [Abstract] [Full Text] [PDF] J. Woodley-Cook, L. Y.Y. Shin, L. Swystun, S. Caruso, S. Beaudin, and P. C. Liaw Effects of the chemotherapeutic agent doxorubicin on the protein C anticoagulant pathway Mol. Cancer Ther., December 1, 2006; 5(12): 3303 - 3311. [Abstract] [Full Text] [PDF] T. Sipahi, H. Pocan, and N. Akar Effect of Various Genetic Polymorphisms on the Incidence and Outcome of Severe Sepsis Clinical and Applied Thrombosis/Hemostasis, January 1, 2006; 12(1): 47 - 54. [Abstract] [PDF] M. V. de Wouwer, D. Collen, and E. M. Conway Thrombomodulin-Protein C-EPCR System: Integrated to Regulate Coagulation and Inflammation Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1374 - 1383. [Abstract] [Full Text] [PDF]

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