| Autor: |
Burkhardt J; Translational Centre for Regenerative Medicine (TRM), Universität Leipzig, Leipzig, Germany., Blume M; University Leipzig, Institute for Clinical Immunology and Tranfusion Medicine (IKIT), Universität Leipzig, Leipzig, Germany., Petit-Teixeira E; Genhotel-EA 3886, Université d'Evry-Val d'Essonne, Evry, France., Hugo Teixeira V; Centre for Respiratory Research, University College London, London, United Kingdom., Steiner A; University Leipzig, Institute for Clinical Immunology and Tranfusion Medicine (IKIT), Universität Leipzig, Leipzig, Germany., Quente E; Fraunhofer Institute for Celltherapy and Immunology (IZI), Leipzig, Germany., Wolfram G; Translational Centre for Regenerative Medicine (TRM), Universität Leipzig, Leipzig, Germany., Scholz M; LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany., Pierlot C; Genhotel-EA 3886, Université d'Evry-Val d'Essonne, Evry, France., Migliorini P; Pisa University, Pisa, Italy., Bombardieri S; Pisa University, Pisa, Italy., Balsa A; La Paz Hospital, Madrid, Spain., Westhovens R; Rheumatology KU Leuven, Leuven, Belgium., Barrera P; Nijmegen University, Nijmegen, the Netherlands., Radstake TR; University Medical Center Utrecht, Utrecht, the Netherlands., Alves H; Porto San Joao Hospital, Porto, Portugal., Bardin T; Fédération de Rhumatologie, Lariboisière Hospital, Paris, France., Prum B; Laboratoire Statistique & Génome, Université d'Evry-Val d'Essonne, Evry, France., Emmrich F; Translational Centre for Regenerative Medicine (TRM), Universität Leipzig, Leipzig, Germany; University Leipzig, Institute for Clinical Immunology and Tranfusion Medicine (IKIT), Universität Leipzig, Leipzig, Germany; Fraunhofer Institute for Celltherapy and Immunology (IZI), Leipzig, Germany., Cornelis F; GenHotel-Auvergne, Université d'Auvergne, Clermont-Ferrand, France., Ahnert P; LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Universität Leipzig, Leipzig, Germany., Kirsten H; Fraunhofer Institute for Celltherapy and Immunology (IZI), Leipzig, Germany; LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Institute for Medical Informatics, Statistics and Epidemiology (IMISE), Universität Leipzig, Leipzig, Germany. |
| Abstrakt: |
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<10-6) 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. |
