Manuel Mattheisen

High factor VIII levels in venous thromboembolism show linkage to imprinted loci on chromosomes 5 and 11

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Mario Berger
  • ,
  • Manuel Mattheisen
  • Bettina Kulle
  • ,
  • Henriette Schmidt
  • ,
  • Johannes Oldenburg
  • ,
  • Heike Bickeböller
  • ,
  • Ulrich Walter
  • ,
  • Tom H Lindner
  • ,
  • Konstantin Strauch
  • ,
  • Christian M Schambeck
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.
Original languageEnglish
JournalBlood
Volume105
Issue2
Pages (from-to)638-44
Number of pages7
ISSN0006-4971
DOIs
Publication statusPublished - 15 Jan 2005

    Research areas

  • Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 5, Factor VII, Female, Genetic Linkage, Genome, Human, Genomic Imprinting, Humans, Male, Microsatellite Repeats, Venous Thrombosis

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