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

Annals of the Rheumatic Diseases
Emma V A RaineJohn Loughlin

Abstract

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. 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. 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 carrier...Continue Reading

Citations

Feb 19, 2013·Expert Reviews in Molecular Medicine·Louise N Reynard, John Loughlin
Dec 20, 2012·Current Opinion in Rheumatology·Marc C HochbergBraxton D Mitchell
Jul 23, 2013·Journal of Medical Genetics·Kalliope Panoutsopoulou, Eleftheria Zeggini
Oct 16, 2015·Human Molecular Genetics·Michael D RushtonJohn Loughlin
Sep 19, 2014·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Godfrey E EtokebeZlatko Dembic
Aug 25, 2012·Osteoarthritis and Cartilage·J B J van Meurs, A G Uitterlinden
Jun 27, 2015·Current Rheumatology Reports·Yolande F M Ramos, Ingrid Meulenbelt
Jul 13, 2013·Osteoarthritis and Cartilage·A Gonzalez
Jul 6, 2014·Reumatología clinica·Cristina Rodriguez-Fontenla, Antonio Gonzalez
May 1, 2016·Seminars in Cell & Developmental Biology·Louise N Reynard
Jan 25, 2017·Nature Communications·Mark S BakerShoba Ranganathan
Jan 27, 2019·Cellular and Molecular Life Sciences : CMLS·Emeline BollaertJean-Baptiste Demoulin

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