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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1280-1283. Prepublished online as a Blood First Edition Paper on May 9, 2006; DOI 10.1182/blood-2006-04-015701. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-015701v1 108/4/1280    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 Zwicker, J. I. Articles by Mannucci, P. Search for Related Content PubMed PubMed Citation Articles by Zwicker, J. I. Articles by Mannucci, P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size Jeffrey I. Zwicker, Flora Peyvandi, Roberta Palla, Rossana Lombardi, Maria Teresa Canciani, Andrea Cairo, Diego Ardissino, Luisa Bernardinelli, Kenneth A. Bauer, Jack Lawler, and Pier Mannucci From the Division of Hematology-Oncology and the Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Maggiore Hospital, Mangiagalli and Regina Elena Foundation and Luigi Villa Foundation, Milan, Italy; Division of Cardiology, Maggiore Hospital, University of Parma, Italy; Dipartimento di Scienze Sanitarie Applicate e Psicocomportamentali, University of Pavia, Italy; and the Medical Research Council Biostatistics Unit, Cambridge, United Kingdom. The N700S polymorphism of thrombospondin-1 (TSP-1) has been identified as a potential genetic risk factor for myocardial infarction (MI). In a large case-control study of 1425 individuals who survived a myocardial infarction prior to age 45, the N700S polymorphism was a significant risk factor for myocardial infarction in both homozygous (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.3, P = .01) and heterozygous carriers of the S700 allele (OR 1.4, 95% CI 1.1-3.3, P = .01). TSP-1 has been shown to reduce von Willebrand factor (VWF) multimer size, and the domain responsible for VWF-reducing activity has been localized to the calcium-binding C-terminal sequence. As the N700S polymorphism was previously shown to alter the function of this domain, we investigated whether the altered VWF-reducing activity of TSP-1 underlies the observed prothrombotic phenotype. The TSP1 N700S polymorphism did not influence VWF multimer size in patients homozygous for either allele nor was there a significant reduction of VWF multimer size following incubation with recombinant N700S fragments or platelet-derived TSP-1. 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