Genes and mediators of inflammation and development in osteoarthritis

Leiden Repository

Genes and mediators of inflammation and development in osteoarthritis

Type: Doctoral Thesis
Title: Genes and mediators of inflammation and development in osteoarthritis
Author: Bos, Steffan Daniël
Publisher: Department of Molecular Epidemiology, Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2010-09-15
Keywords: Association
CRP
Cytokines
Genes
Immunohistochemistry
Inflammation
Linkage
Osteoarthritis
Abstract: Osteoarthritis (OA) mainly affects the articular cartilage covering the bones. In this thesis we investigated the relation between levels of inflammatory mediators, genes involved in their regulation and the disease status of OA. We investigated the role of genetic variation at the interleukin(IL)-1 gene cluster in the innate bio-availability of IL-1beta. A haplotype that associated to low innate bio-availability also associated to higher hand OA scores. Although this is counterintuitive with respect to the generally accepted hypothesis that a pro-inflammatory status is detrimental to the cartilage it underlines a complex relationship between inflammation and OA. For the C-reactive protein we identified a haplotype associated to high CRP levels as well as to severe hand OA, which is more in line with expected directions of associations. Analysis of baseline cytokine and chemokine levels indicated that chemokine levels associated to hand OA scores, again with low levels associated to high OA scores. In a follow up functional genomic analysis of a previously identified OA susceptibility gene (DIO2) in our studies we show that the risk allele of this gene is transcribed at higher levels as compared to the non-risk allele. Furthermore, we showed increased DIO2 protein presence in OA affected cartilage.
Description: Promotor: P.E. Slagboom, Co-promotor: I. Meulenbelt
With summary in Dutch
Faculty: LUMC
Citation: Bos, S.D., 2010, Doctoral thesis, Leiden University
ISBN: 9789461080769
Sponsor: Project van het Reumafonds
Handle: http://hdl.handle.net/1887/15944
 

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