Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression
2014
Burkhardt, Jana | Blume, Mechthild | Petit-Teixeira, Elisabeth | Hugo Teixeira, Vitor | 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 | Cornélis, François | Ahnert, Peter | Kirsten, Holger | Translational Centre for Regenerative Medicine (TRM); Department of Cell Therapy ; Translational Centre for Regenerative Medicine (TRM); Department of Cell Therapy ; Leipzig University / Universität Leipzig-Leipzig University / Universität Leipzig | Leipzig University / Universität Leipzig | Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel) ; Université d'Évry-Val-d'Essonne (UEVE) | University College of London [London] (UCL) | Institute for Medical Informatics ; Institute for Medical Informatics | University of Pisa [Italy] = Università di Pisa [Italia] = Université de Pise [Italie] (UniPi) | University Hospital La Paz, Madrid ; University Hospital La Paz, Madrid | Technologie campus Gent - KU Leuven (KU Leuven) | Radboud University [Nijmegen] | University Medical Center [Utrecht] (UMCU) | Unité de Génétique Clinique Adulte ; Hôpital Lariboisière-Fernand-Widal [APHP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) | Laboratoire Statistique et Génome (LSG) ; Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)
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Показать больше [+] Меньше [-]Английский. 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\backslashtextless10-6) 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.
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