Citation
Uitte de Willige, S. (2007, May 23). Novel genetic risk factors for venous
thrombosis; a haplotype-based candidate gene approach. Hemostasis and
Thrombosis Research Center, Department of Hematology, Faculty of Medicine,
Leiden University. Retrieved from https://hdl.handle.net/1887/11970
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis
in the Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/11970
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Novel genetic risk factors for venous thrombosis;
a haplotype-based candidate gene approach
Novel genetic risk factors for venous thrombosis;
a haplotype-based candidate gene approach
PROEFSCHRIFT
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus prof. mr. P.F. van der Heijden, volgens besluit van het College voor Promoties
te verdedigen op 23 mei 2007 klokke 15:00 uur
door
Shirley Uitte de Willige geboren te Den Haag
in 1978
Promotores: Prof. dr. R.M. Bertina
Prof. dr. F.R. Rosendaal
Co-promotor: Dr. M.C.H. de Visser
Referent: Dr. R.A.S. Ariëns (University of Leeds)
Overige leden: Prof. dr. P.E. Slagboom Prof. dr. R.G. Westendorp Prof. dr. T.W. Huizinga
The research described in this thesis was financially supported by a grant of the Netherlands Organization for Scientific Research (NWO, grant 912-02-036) and was performed at the Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center, the Netherlands.
Financial support by the Netherlands Heart Foundation and the J.E. Jurriaanse Stichting for the publication of this thesis is gratefully acknowledged.
Additional support was kindly provided by the Dr. Ir. Van de Laar Stichting and Eurogentec.
Coverdesign: Aat van Wijngaarden
© 2007 S. Uitte de Willige ISBN: 978-90-9021729-1
Printed by Printpartners Ipskamp, Enschede, the Netherlands
‘Het leven is wat je gebeurt terwijl je andere plannen maakt’
Acda & de Munnik (origineel van John Lennon)
Voor jou, pap
Table of Contents
page Chapter 1
General Introduction 11
Chapter 2
Haplotypes of the EPCR gene, plasma sEPCR levels and the risk of deep venous thrombosis
25
Chapter 3 Fibrinogen
3.1 Genetic variation in the fibrinogen gamma gene increases the risk of deep venous thrombosis by reducing plasma fibrinogen γ' levels
41
3.2 Polymorphism 10034C>T is located in a region regulating polyadenylation of FGG transcripts and influences the fibrinogen γ'/γA mRNA ratio.
63
3.3 Polymorphisms in the 3’-end of the fibrinogen gamma gene and risk of venous thromboembolism in the African-American and Caucasian population
79
3.4 Haplotypes of the fibrinogen gamma gene do not affect the risk of myocardial infarction
93 3.5 Fibrinogen gamma in ischemic stoke: a case-control study 101
Chapter 4
Selectin haplotypes and the risk of deep venous thrombosis;
Influence of linkage disequilibrium with the Factor V Leiden mutation
115
Chapter 5
General Discussion and Summary 133
Samenvatting 155 Publications and Abstracts 165
Nawoord 171
Curriculum Vitae 175
