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Blood, 15 January 2005, Vol. 105, No. 2, pp. 638-644. Prepublished online as a Blood First Edition Paper on September 7, 2004; DOI 10.1182/blood-2004-05-2018. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-2018v1 105/2/638    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 Berger, M. Articles by Schambeck, C. M. Search for Related Content PubMed PubMed Citation Articles by Berger, M. Articles by Schambeck, C. M. 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 High factor VIII levels in venous thromboembolism show linkage to imprinted loci on chromosomes 5 and 11 Mario Berger, Manuel Mattheisen, Bettina Kulle, Henriette Schmidt, Johannes Oldenburg, Heike Bickeböller, Ulrich Walter, Tom H. Lindner, Konstantin Strauch, and Christian M. Schambeck From the Medical Department, and the Blood Coagulation Unit and Central Laboratory, Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany; the Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany; the Department of Genetic Epidemiology, University of Göttingen, Göttingen, Germany; and the Deutsches Rotes Kreuz (DRK) Blood Donor Service Baden-Württemberg-Hessen, Frankfurt, Germany. High factor VIII (FVIII) levels are known to be a risk factor for deep venous thrombosis, but the mechanisms responsible for high FVIII levels remain unclear. Here, a new phenotype "FVIII level residuum" (FVIII-R) was defined in order to eliminate the impact of common determinants on FVIII levels. We studied 13 families of patients with thrombosis and reproducibly high FVIII levels of unknown origin. Since familial clustering was evident, we looked for a possible genetic basis. A genome scan was performed with 402 evenly spaced microsatellite markers. A quantitative linkage analysis using variance component methods showed suggestive evidence for linkage of FVIII-R with a locus on chromosome 8 (logarithm of odds [LOD] = 2.1). In addition, we performed parametric exploratory linkage analysis of dichotomized FVIII-R, taking a parent-of-origin effect into account. Single-trait-locus MOD-score analysis showed suggestive evidence for linkage under an imprinting model at chromosomes 5 and 11. Furthermore, a 2-trait-locus analysis under a multiplicative model for the loci of chromosomes 5 and 11 yielded a remarkable LOD of 4.44. It confirmed the finding of paternal imprinting, obtained by single-trait-locus analysis, at both loci. Our results suggest that high FVIII levels in venous thromboembolism represent a complex trait caused by several genetic factors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. R. Viel, D. K. Machiah, D. M. Warren, M. Khachidze, A. Buil, K. Fernstrom, J. C. Souto, J. M. Peralta, T. Smith, J. Blangero, et al. A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels Blood, May 1, 2007; 109(9): 3713 - 3724. [Abstract] [Full Text] [PDF] P. P. Luedi, A. J. Hartemink, and R. L. Jirtle Genome-wide prediction of imprinted murine genes Genome Res., June 1, 2005; 15(6): 875 - 884. [Abstract] [Full Text] [PDF]

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