Ann Rheum Dis 71:2020-2027 doi:10.1136/annrheumdis-2012-201304
  • Clinical and epidemiological research
  • Extended report

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

  1. J Loughlin
  1. Institute of Cellular Medicine, Musculoskeletal Research Group, Newcastle University, Newcastle-upon-Tyne, UK
  1. Correspondence to Emma Raine, Newcastle University, Musculoskeletal Research Group, 4th floor Catherine Cookson Building, Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK; e.v.a.raine{at}
  1. Contributors All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. JL had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: ER and JL. Acquisition of data: ER, NW, AWD. Analysis and interpretation of data: ER, NW, LNR and JL.

  • Accepted 9 April 2012
  • Published Online First 14 May 2012


Objectives An osteoarthritis (OA) susceptibility locus has been mapped to chromosome 7q22, to a region of high-linkage disequilibrium encompassing six genes: PRKAR2B, HBP1, COG5, GPR22, DUS4L and BCAP29. The authors assessed whether these genes were subject to cis-acting regulatory polymorphisms that are active in joint tissues and which could contribute to the association signal.

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).

Conclusion Cis-acting regulatory polymorphisms acting on HBP1 contribute to the 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.


  • Funding Arthritis Research UK and UK NIHR Biomedical Research Centre for Ageing and Age-related disease.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it was published Online First.