Generalised osteoarthritis: from Mendelian disorder to complex disease

Leiden Repository

Generalised osteoarthritis: from Mendelian disorder to complex disease

Type: Doctoral Thesis
Title: Generalised osteoarthritis: from Mendelian disorder to complex disease
Author: Min, Josine Louise
Publisher: Department of Molecular Epidemiology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2007-01-17
Keywords: Generalised osteoarthritis
FRZB
MATN3
DIO2
IDH1
NRP2
Mutation screening
Genome wide scan
Association analysis
Linkage analysis
Abstract: Osteoarthritis (OA) is a prevalent and complex disorder with a high hereditary probability. Previous genetic research into OA has yielded several common gene variants contributing to joint specific OA phenotypes. Only a few studies allowed an examination of multiple joint sites in the patients included. In this thesis, we have focused, on the identification and investigation of OA susceptibility of rare and common generalised OA (GOA) in family based studies and common OA in the population. We investigated previously reported relationships between two candidate genes (FRZB and MATN3) with OA in a random sample from the population-based Rotterdam study and in siblings from the Genetics Osteoarthritis and Progression (GARP) study. A functional variant in FRZB indeed associates to OA but this seems not confined to hip only. Associations of MATN3 variants suggest that genetic variation in this gene determines susceptibility to spinal disc degeneration and OA of the first carpometacarpal joint. Different linkage areas were identified for early and late onset GOA. We mapped a major locus for OA at multiple joint sites on 14q32.11 in middle aged siblings from the GARP study and on 2q33.3 in seven early onset families. From our studies so far, DIO2, IDH1 and NRP2 may be new OA loci.
Description: Promotores: P.E. Slagboom, C.M. van Duijn, Co-promotor: I. Meulenbelt
With Summary in Dutch
Faculty: LUMC
Citation: Min, J.L., 2007, Doctoral Thesis, Leiden University
ISBN: 9789064640544
9064640548
Sponsor: Netherlands Organisation for Scientific Research (grant 904-61-095)
Handle: http://hdl.handle.net/1887/8782
 

Files in this item

Description Size View
text/html Links to published articles 7.952Kb View/Open
application/pdf Cover 133.8Kb View/Open
application/pdf Title page_Contents 29.69Kb View/Open
application/pdf Chapter 1 3.523Mb View/Open
application/pdf Chapter 2 492.9Kb View/Open
application/pdf Chapter 3.1 86.64Kb Under embargo
application/pdf Chapter 3.2 137.0Kb View/Open
application/pdf Chapter 4 843.8Kb View/Open
application/pdf Chapter 5.1 975.4Kb View/Open
application/pdf Chapter 5.2 634.9Kb View/Open
application/pdf Summary in English and General Discussion 157.8Kb View/Open
application/pdf Summary in Dutch 67.39Kb View/Open
application/pdf Curriculum Vitae_Acknowledgements 26.89Kb View/Open
application/pdf Propositions 41.99Kb View/Open

This item appears in the following Collection(s)