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  RA-specific expression profiles and new candidate genes

Ungethuem, U., Haeupl, T., Koczan, D., Huber, H., von Helversen, T., Ruiz, P., et al. (2003). RA-specific expression profiles and new candidate genes. /: BioMed Central.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8AAC-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8AAD-C
Genre: Proceedings

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 Creators:
Ungethuem, U., Author
Haeupl, T., Author
Koczan, D., Author
Huber, H., Author
von Helversen, T., Author
Ruiz, Patricia1, Author
Witt, Henning1, Author
Drungowski, Mario1, Author
Zacher, H. J., Author
Seyfert, C., Author
Neidel, J., Author
Krenn, V., Author
Burmester, G. R., Author
Thiesen, H. J., Author
Lehrach, Hans2, Author              
Blaess, S., Author
Affiliations:
1Max Planck Society, ou_persistent13              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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 Abstract: Objective: To identify rheumatoid arthritis- (RA)-specific profiles of differentially expressed genes. Methods: Synovial tissues from RA and osteoarthritis (OA) patients and from normal joints were selected according to their disease-characteristic histology. Gene expression was analyzed using DNA microarrays (GeneChip; Unigene-array) and representational difference analysis (RDA). Data were validated on larger cohorts of patients by RT-PCR. Results: Nine hundred and eighty genes were significantly regulated in RA synovial tissue as compared with non-RA. Specialized cluster analysis identified a set of 312 genes as sufficient of unequivocally discriminating RA from non-RA patterns (class discovery). Genes of highest regulation were associated with leukocyte activation (chemokines, chemokine receptors, B- and T-cell genes), endothelial and angiogenic activation, tissue destruction and remodelling [MMP-3, BMP-4, TIMPs]. Interestingly, a large set of genes was down-regulated in RA (TGF-β superfamily, apoptosis-related genes, transcription factors). Osteopontin-like genes (n=46) — up-regulated in RA — and glutathione peroxidase-3-like genes (n=85) — down-regulated in RA — yielded the highest correlation coefficients (>0.94). Megakaryocyte stimulating factor (MSF), down-regulated in a subset of RA, may hold the key to subclassification: a loss-of-function mutation in the MSF-encoding gene leads to synovial hyperplasia in camptodactyly–arthropathy–coxa vara–pericarditis syndrome, and, as in RA, also to pericardial involvement. A further candidate, vitamin-D3-up-regulated protein-1 (VDUP-1), is regulated like MSF and predisposes to premature coronary artery disease when mutated, again a feature of a subset of RA. Conclusion: RA specific gene profiles were identified and are useful to improve diagnostics of the disease. Novel gene candidates not yet in the focus of RA pathogenesis have been identified that are likely to further the understanding of RA.

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Language(s): eng - English
 Dates: 2003-02-24
 Publication Status: Published in print
 Pages: /
 Publishing info: / : BioMed Central
 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 175486
ISI: 000189109200082
ISSN: 1478-6362
 Degree: -

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Title: 23rd European Workshop for Rheumatology Research
Place of Event: Marseille, France
Start-/End Date: -

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