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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



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ID: 548980.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis.
Authors:Ungethuem, U.; Haeupl, T.; Witt, H.; Koczan, D.; Krenn, V.; Huber, H.; von Helversen, T. M.; Drungowski, M.; Seyfert, C.; Zacher, J.; Pruss, A.; Neidel, J.; Lehrach, H.; Thiesen, H. J.; Ruiz, P.; Blaess, S.
Language:English
Research Context:This project was supported by the Deutsche Forschungsgemeinschaft (HA2267/2-3) and the German Ministry of Research (BMBF) by several grants: Kompetenznetz Rheuma, TPD6; FKZo1GG9831; NGFN/BerlInflame.
Date of Publication (YYYY-MM-DD):2010-09-21
Title of Journal:Physiological Genomics
Journal Abbrev.:Physiol Genomics
Volume:42A
Issue / Number:4
Start Page:267
End Page:282
Copyright:© 2010 the American Physiological Society
Review Status:not specified
Audience:Experts Only
Abstract / Description:Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover pathomechanisms, we performed genome-wide gene expression analysis. We identified a set of 1054 genes significantly deregulated in pair-wise comparisons between RA and osteoarthritis (OA) patients, RA and normal donors (ND), or OA and ND. Correlation analysis revealed gene sets regulated identically in all three groups. As a prominent example secreted phosphoprotein 1 (SPP1) was identified to be significantly upregulated in RA as compared to both OA and ND. SPP1 expression was found to correlate with genes expressed during an inflammatory response, T cell activation and apoptosis, suggesting common underlying regulatory networks. A sub-classification of RA patients was achieved on the basis of proteoglycan 4 (PRG4) expression distinguishing PRG4 high- and low expressors and reflecting the heterogeneity of the disease. In addition, we found that low PRG4 expression was associated with a more aggressive disease stage, which is in accordance with PRG4 loss-of-function mutations causing camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Altogether we provide evidence for molecular signatures of RA and RA subclasses, sets of new candidate genes as well as for candidate gene networks, which extend our understanding of disease mechanisms and may lead to an improved diagnosis.
Free Keywords:gene expression
synovium
secreted phosphoprotein 1
proteoglycan 4
Comment of the Author/Creator:correspondence: U. Ungethuem, Charité Universitätsmedizin Berlin, Laboratory of Functional Genome Research, Charitéplatz 1, 10117 Berlin, Germany
e-mail: Ute.Ungethuem@Charite.de
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Laboratory of Functional Genome Research,
2.Department of Rheumatology and Clinical Immunology,
3.Center for Cardiovascular Research, Charité Universitätsmedizin Berlin, Berlin, Germany;
4.Proteome Center Rostock, Institute of Immunology, Rostock, Germany;
5.Institute for Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany;
6.Orthopedic Clinic, Kyritz;
7.Orthopedic Department, HELIOS Hospital;
8.Transfusion Medicine (Tissue Bank),
9.Orthopedic Clinic, Charité Universitätsmedizin Berlin, Berlin, Germany.
Identifiers:ISSN:1094-8341 [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=... [ID No:2]
DOI:10.1152/physiolgenomics.00004.2010 [ID No:3]
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