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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2149. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2149v1 101/5/1833    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 Dupont, A. Articles by Gaussem, P. Search for Related Content PubMed PubMed Citation Articles by Dupont, A. Articles by Gaussem, P. Related Collections Signal Transduction Gene Expression Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2003, Vol. 101, No. 5, pp. 1833-1840 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY An intronic polymorphism in the PAR-1 gene is associated with platelet receptor density and the response to SFLLRN Annabelle Dupont, Pierre Fontana, Christilla Bachelot-Loza, Jean-Luc Reny, Ivan Bièche, Florence Desvard, Martine Aiach, and Pascale Gaussem From the Service d'Hématologie Biologique and INSERM Unité 428, Hôpital Européen Georges Pompidou, and Laboratoire de Génétique Moléculaire, UPRES-JE 2195, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris, France. Protease-activated receptor 1 (PAR-1), the main thrombin receptor on vascular cells, plays a key role in platelet activation. We examined the range of PAR-1 expression on platelets, obtained twice, 1 week apart, from 100 healthy subjects and found a 2-fold interindividual variation in receptor numbers (95% CI = 858-1700). Because PAR-1 density was stable with time (r2 = 76%, P < .001), we sought a genetic explanation for the observed variability. To validate this approach, we also analyzed the 21 genotype according to receptor density and platelet mRNA expression data. We found that the number of PAR-1 receptors on the platelet surface is associated with the intervening sequence IVSn14 A/T intronic variation. The number of receptors was also found to govern the platelet response to the SFLLRN agonist, in terms of aggregation and P-selectin expression. The T allele (allelic frequency, 0.14) can be considered as an allele with decreased expression, because it was associated with lower PAR-1 expression on the platelet surface and with a lower response to SFLLRN. The IVSn14 A/T intronic variation may therefore be clinically relevant. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] K. V. Vijayan and P. F. 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