Gene expression analysis reveals HBP1 as a key target for the osteoarthritis susceptibility locus that maps to chromosome 7q22
Annals of Rheumatic Diseases,

Raine EVA et al. – Cis–acting regulatory polymorphisms acting on HBP1 contribute to the osteoarthritis (OA) association signal at chromosome 7q22. HBP1 codes for a transcription factor and studies by the authors have enabled them to prioritise this gene for further investigation.

Methods
  • Using joint tissues from 156 patients with OA, and control cartilage from 25 patients who had neck of the femur fractures, the authors measured the overall gene expression by quantitative PCR and the allelic expression of the genes, using an assay that can distinguish mRNA output from each allele of a transcript single nucleotide polymorphism.

Results
  • Five of the genes were expressed in joint tissues, the exception being GPR22, which the authors could not detect.
  • In OA cartilage compared with control cartilage, significantly reduced expression levels were observed for these five genes.
  • Carriers of the OA–associated alleles showed a significant reduction in expression of HBP1 in cartilage (p=0.0002) and synovium (p=0.02), and of DUS4L in fat pad (p=0.04).
  • HBP1 and DUS4L also demonstrated allelic expression imbalance across a range of different joint tissues, with carriers of the associated allele showing an HBP1 allelic expression imbalance profile that was significantly different from non–carriers (p=0.008).

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