Matrix metalloproteinase-3 (Stromelysin-1) gene promotor polymorphism in relation to predisposition to inflammatory bowel disease (IBD)
Matrix metalloproteinase-3 (Stromelysin-1) gene promotor polymorphism in relation to predisposition to inflammatory bowel disease (IBD)
The aims of this study were to investigate MMP-3 production between individuals with different MMP-3 5A/6A genotypes: and to compare the association of the MMP-3 5A/6A genotype with susceptibility to CD and UC.
Myofibroblast cell lines were isolated from CD, UC patients and control subjects. The phenotype of these cells lines were characterised with immunohistochemistry. Cell lines were stimulated with TNF-α or IL-1β and the production of MMP-3 was measured by western blotting and ELISA.
Cell lines from CD, UC and control patients were myofibroblast-enriched populations of cells. Cell lines responded to stimulation with TNF-α by a dose-dependent rise in MMP-3 production. The 5A/6A polymorphism was analysed in 468 German sporadic inflammatory disease trios and 270 British and German multiplex IBD families using the transmission disequilibrium test (TDT). There was an overtransmission of the 5A allele to affected offspring (p=0.0012). There as an interaction between the MMP-3 gene 5A/6A polymorphism and the Caspase Activating Recruitment Domain (CARD) 15 gene, a well established gene for CD, such that overtransmission of the 5A allele was a significant in CARD15 carriers (p=0.0054) but not in non-carriers. In the CARD15 carriers, overtransmission of the 5A allele was associated with stenosis (p=0.0027), fistulising disease (p=0.007), previous surgical resection (p=0.0023), disease of the ileum (p=0.0001), and disease of the right colon (p=0.0015) in CD. The relationship of functional polymorphisms in promoters of the MMP-1,-3,-9 and -12 genes with IBD was also investigated in children and adults, and age-matched controls. No significant association was found between these polymorphisms and CD or UC, though the power of these studies was reduced by small sample numbers. In conclusion, the MMP-3 5A/6A polymorphism appears to be a genetic factor in CD.
University of Southampton
Prothero, Joanna
a42a55c7-4b0f-452d-89ec-9c161afd9dc1
2006
Prothero, Joanna
a42a55c7-4b0f-452d-89ec-9c161afd9dc1
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Prothero, Joanna
(2006)
Matrix metalloproteinase-3 (Stromelysin-1) gene promotor polymorphism in relation to predisposition to inflammatory bowel disease (IBD).
University of Southampton, Doctoral Thesis, 184pp.
Record type:
Thesis
(Doctoral)
Abstract
The aims of this study were to investigate MMP-3 production between individuals with different MMP-3 5A/6A genotypes: and to compare the association of the MMP-3 5A/6A genotype with susceptibility to CD and UC.
Myofibroblast cell lines were isolated from CD, UC patients and control subjects. The phenotype of these cells lines were characterised with immunohistochemistry. Cell lines were stimulated with TNF-α or IL-1β and the production of MMP-3 was measured by western blotting and ELISA.
Cell lines from CD, UC and control patients were myofibroblast-enriched populations of cells. Cell lines responded to stimulation with TNF-α by a dose-dependent rise in MMP-3 production. The 5A/6A polymorphism was analysed in 468 German sporadic inflammatory disease trios and 270 British and German multiplex IBD families using the transmission disequilibrium test (TDT). There was an overtransmission of the 5A allele to affected offspring (p=0.0012). There as an interaction between the MMP-3 gene 5A/6A polymorphism and the Caspase Activating Recruitment Domain (CARD) 15 gene, a well established gene for CD, such that overtransmission of the 5A allele was a significant in CARD15 carriers (p=0.0054) but not in non-carriers. In the CARD15 carriers, overtransmission of the 5A allele was associated with stenosis (p=0.0027), fistulising disease (p=0.007), previous surgical resection (p=0.0023), disease of the ileum (p=0.0001), and disease of the right colon (p=0.0015) in CD. The relationship of functional polymorphisms in promoters of the MMP-1,-3,-9 and -12 genes with IBD was also investigated in children and adults, and age-matched controls. No significant association was found between these polymorphisms and CD or UC, though the power of these studies was reduced by small sample numbers. In conclusion, the MMP-3 5A/6A polymorphism appears to be a genetic factor in CD.
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Published date: 2006
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Local EPrints ID: 466063
URI: http://eprints.soton.ac.uk/id/eprint/466063
PURE UUID: c4434aa4-0a89-436a-bffb-4a24714aa7bd
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Date deposited: 05 Jul 2022 04:12
Last modified: 17 Mar 2024 02:52
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Author:
Joanna Prothero
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