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Title: Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression
Authors: 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, Rene
Barrera, Pilar
Radstake, Timothy R D J
Alves, Helena
Bardin, Thomas
Prum, Bernard
Emmrich, Frank
Cornelis, François
Ahnert, Peter
Kirsten, Holger #
Issue Date: 2014
Series Title: PloS one vol:9 issue:8 pages:e103872
Article number: 10.1371/journal.pone.0103872
Abstract: 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.
URI: 
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Skeletal Biology and Engineering Research Center (+)
× corresponding author
# (joint) last author

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