In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407). Additionally, we investigated differential allelic expression, a possible functional
consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003). This allele was also expressed preferentially (p,1026) with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1 = 0.004; p2 = 0.0177). Evidence for influence of rs6136 on transcription factor binding was also
found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:15-qucosa-151575 |
| Date | 05 September 2014 |
| Creators | Burkhardt, Jana, Blume, Mechthild, Petit-Teixeira, Elisabeth, Teixeira, Vitor Hugo, Steiner, Anke, Quente, Elfi, Wolfram, Grit, Scholz, Markus, Pierlot, Céline, Migliorini, Paola, Bombardieri, Stefano, Balsa, Alejandro, Westhovens, René, Barrera, Pilar, Radstake, Timothy R. D. J., Alves, Helena, Bardin, Thomas, Prum, Bernard, Emmrich, Frank, Cornelis, Francois, Ahnert, Peter, Kirsten, Holger |
| Contributors | Universität Leipzig, Medizinische Fakultät, Universität Leipzig, Medizinische Fakultät, Université d\\\'Evry-Val d\\\'Essonne, Genhotel-EA 3886, University College London, Centre for Respiratory Research, Fraunhofer-Institut für Zelltherapie und Immunologie,, Universität Leipzig, Medizinische Fakultät, Pisa University,, La Paz Hospital,, KU Leuven, Rheumatology, Nijmegen University,, University Medical Center,, Porto San Joao Hospital,, Public Library of Science, |
| Publisher | Universitätsbibliothek Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:article |
| Format | application/pdf |
| Source | Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression. PLoS ONE 9(8): e103872. doi:10.1371/journal.pone.0103872 |
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