title: Gene expression analysis reveals HBP1 as a key target for the osteoarthritis susceptibility locus that maps to chromosome 7q22.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Newcastle University, Musculoskeletal Research Group, 4th floor Catherine Cookson Building, Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK. e.v.a.raine@ncl.ac.uk
authors.forename: E V A
authors.initials: EV
authors.lastname: Raine
authors.forename: N
authors.initials: N
authors.lastname: Wreglesworth
authors.forename: A W
authors.initials: AW
authors.lastname: Dodd
authors.forename: L N
authors.initials: LN
authors.lastname: Reynard
authors.forename: J
authors.initials: J
authors.lastname: Loughlin
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002897:Chromosomes, Human, Pair 7; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006609:High Mobility Group Proteins / Q000235:genetics*; D006621:Hip Joint / Q000473:pathology; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000235:genetics* / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000473:pathology; D010088:Oxidoreductases / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C486244:BCAP29 protein, human; C115632:COG5 protein, human; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; C531500:GPR22 protein, human; C486328:HBP1 protein, human; D006609:High Mobility Group Proteins; D008565:Membrane Proteins; C517837:PRKAR2B protein, human; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; D010088:Oxidoreductases