Expression analysis of the osteoarthritis genetic susceptibility locus mapping to an intron of the MCF2L gene and marked by the polymorphism rs11842874

• DOI: 10.1186/s12881-015-0254-2
• Publication Date: 2015-11-19T07:13:51Z
• Authors: Colin Shepherd; Andrew J. Skelton; Michael D. Rushton; Louise N. Reynard; John Loughlin
• Keywords: Linkage Disequilibrium; SNP

Osteoarthritis (OA) is a painful, debilitating disease characterised by loss of articular cartilage with concurrent changes in other tissues the synovial joint. Genetic association studies have shown that number common variants increase risk developing OA. Investigating their activity can uncover novel causal pathways and potentially highlight new treatment targets. One reported OA signals marked single nucleotide polymorphism (SNP) rs11842874 at chromosome 13q34. positioned within small linkage disequilibrium (LD) block intron 4 MCF2L, gene encoding guanine-nucleotide exchange factor DBS. There are no non-synonymous SNPs correlate this signal we therefore set out to assess whether its effect on susceptibility mediated alteration MCF2L expression. Nucleic acid was extracted from cartilage, membrane or infrapatellar fat pad patients. Expression measured quantitative PCR RNA-sequencing whilst presence DBS studied using immunohistochemistry. The functional 13q34 locus assessed public databases vitro luciferase reporter analysis. protein expression detectable joint tissues, differences transcript isoforms expressed between tested. an trait (eQTL) operating tissue, possession risk-conferring A allele correlating increased LD reside transcriptional regulatory elements direct analysis reveals several show allelic level. subject cis-acting eQTL correlates signal. This contains could account for which merit further investigation. As far as aware, first example tissue but not cartilage.