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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2359-2367. Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2004-01-0349. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0349v1 104/8/2359    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 Kunicki, T. J. Articles by Peake, I. R. Search for Related Content PubMed PubMed Citation Articles by Kunicki, T. J. Articles by Peake, I. R. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY An association of candidate gene haplotypes and bleeding severity in von Willebrand disease (VWD) type 1 pedigrees Thomas J. Kunicki, Augusto B. Federici, Daniel R. Salomon, James A. Koziol, Steven R. Head, Tony S. Mondala, Jeffrey D. Chismar, Luciano Baronciani, Maria Teresa Canciani, and Ian R. Peake From the Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Division of Biostatistics of the Department of Molecular and Experimental Medicine, and the DNA Array Core Facility of The Scripps Research Institute, La Jolla, CA; Department of Internal Medicine and Dermatology, IRCCS Maggiore Hospital and University of Milan, Italy; and Division of Genomic Medicine, Royal Hallamshire Hospital, Sheffield, United Kingdom. von Willebrand disease (VWD) type 1 is difficult to diagnose because of bleeding variability and low heritability of von Willebrand factor (VWF) levels. We compared a bleeding severity score and bleeding times to candidate gene haplotypes within pedigrees of 14 index cases, using a covariance components model for multivariate traits (Mendel: QTL Association). These pedigrees included 13 affected and 40 unaffected relatives, as defined by plasma ristocetin cofactor (VWF:RCo) levels. The bleeding severity score was derived from a detailed history. Donors were genotyped using a primer extension method, and 9 candidate genes were selected for analysis. VWF:RCo levels had the strongest influence on bleeding severity score and bleeding time. ITGA2 haplotype 2 (807C) and ITGA2B haplotype 1 (Ile843) were each associated with increased bleeding severity scores (P < .01 and P < .01, respectively). GP6 haplotype b (Pro219) was also associated with increased scores (P = .03) after adjustment for donor age. No association was observed with 6 other candidate genes, GP1BA, ITGB3, VWF, FGB, IL6, or TXA2R. Increased plasma VWF:Ag levels were associated with VWF haplotype 1 (–1793G; P = .02). These results establish that genetic differences in the adhesion receptor subunits 2, IIb, and GPVI can influence the phenotype of VWD type 1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Goodeve, J. Eikenboom, G. Castaman, F. Rodeghiero, A. B. Federici, J. Batlle, D. Meyer, C. Mazurier, J. Goudemand, R. Schneppenheim, et al. Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD) Blood, January 1, 2007; 109(1): 112 - 121. [Abstract] [Full Text] [PDF] J. P. Riddel Jr. and B. E. Aouizerat Genetics of von Willebrand disease type 1. Biol Res Nurs, October 1, 2006; 8(2): 147 - 156. [Abstract] [PDF] D. L. Yee, C. W. Sun, A. L. Bergeron, J.-f. Dong, and P. F. Bray Aggregometry detects platelet hyperreactivity in healthy individuals Blood, October 15, 2005; 106(8): 2723 - 2729. [Abstract] [Full Text] [PDF]

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