Title: |
Transcription profiling of human rheumatoid arthritis patients to identify inter-individual and gene-specific variance in the synovial membrane
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Organism(s): |
Homo sapiens
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Description: |
Background. Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease, characterized by overexpression of pro-inflammatory/-destructive genes and other activating genes (e.g., proto-oncogenes) in the synovial membrane (SM). The gene expression in disease is often characterized by significant inter-individual variances via specific synchronization/desynchronization of gene expression. To elucidate the contribution of the variance to the pathogenesis of disease, expression variances were tested in SM samples of RA patients, osteoarthritis (OA) patients, and normal controls (NC). Results. For the comparison between RA and NC, 568 genes with significantly different variances in the 2 groups (p < 0.05; Bonferroni/Holm corrected Brown-Forsythe version of the Levene-Test) were selected. For the comparison between RA and OA, 333 genes were selected. Using the Kyoto encyclopedia of genes and genomes (KEGG), 10 pathways/complexes significantly affected by higher gene expression variances were identified in RA compared to NC, including cytokine-cytokine receptor interactions, the TGF-pathway, and anti-apoptosis. Compared to OA, 3 pathways with significantly higher variances were identified in RA (e.g., B cell receptor signaling, VEGF signaling). Functionally, the majority of the identified pathways is involved in the regulation of inflammation, proliferation, cell survival, and angiogenesis. Conclusion. In RA, a number of disease-relevant or even disease-specific pathways/complexes are characterized by broad intra-group, inter-individual expression variances. This indicates that RA pathogenesis in different individuals may depend to a lesser extent on common alterations of the expression of specific key genes, but on individual-specific alterations of different genes resulting in common disturbances of key pathways. Experiment Overall Design: Expression variances were tested in synovial membrane samples of rheumatoid arthritis patients, osteoarthritis patients, and normal controls (see publication for further details).
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Design(s): |
unknown_experiment_design_type, transcription profiling by array
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Experimental factor(s): |
Current NSAID
3
recorded
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non-steroidal anti-inflammatory drug
sulfasalazine
cyclooxygenase 2 inhibitor
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current steroid
1
recorded
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prednisolone
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Current NSARD
1
recorded
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antirheumatic drug
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disease
3
recorded
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osteoarthritis
Healthy_control_subjects
rheumatoid arthritis
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current drug
3
recorded
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methotrexate
Tilidine (CHEMBL563449)
hydroxychloroquine
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Publication(s): |
Hummert Huber, Pohlers Gausmann, Guthke Koczan, Kinne
Identification of intra-group, inter-individual, and gene-specific variances in mRNA expression profiles in the rheumatoid arthritis synovial membrane.
PubMed:18721452
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Sample attribute(s): |
Material Type
2
recorded
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|
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synthetic_RNA
total_RNA
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sex
2
recorded
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female
male
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age
23
recorded
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|
|
76
75
80
66
29
71
62
17
47
64
53
46
36
78
39
73
79
65
77
61
63
59
88
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sample type
1
recorded
|
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Surgical excision sample
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tissue
1
recorded
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synovium
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Label
1
recorded
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biotin
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organism
1
recorded
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Homo sapiens
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Contact(s): |
René Huber
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Release Date: |
10/25/2008
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Submission Date: |
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Metadata Downloads |
Download Study Metadata as ISAtabDownload Study Metadata as ISAtab
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Assay Downloads |
transcription profiling using DNA microarray
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57 assays |
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