title: Dupuytren's disease susceptibility gene, EPDR1, is involved in myofibroblast contractility.
abstract: BACKGROUND
  Dupuytren's Disease is a common disorder of the connective tissue characterized by progressive and irreversible fibroblastic proliferation affecting the palmar fascia. Progressive flexion deformity appears over several months or years and although usually painless, it can result in a serious handicap causing loss of manual dexterity. There is no cure for the disease and the etiology is largely unknown. A genome-wide association study of Dupuytren's Disease identified nine susceptibility loci with the strongest genetic signal located in an intron of EPDR1, the gene encoding the Ependymin Related 1 protein.
  
  
  OBJECTIVE
  Here, we investigate the role of EPDR1 in Dupuytren's Disease.
  
  
  METHODS
  We research the role of EPDR1 by assessing gene expression in patient tissue and by gene silencing in fibroblast-populated collagen lattice (FPCL) assay, which is used as an in vitro model of Dupuytren's contractures.
  
  
  RESULTS
  The three alternative transcripts produced by the EPDR1 gene are all detected in affected Dupuytren's tissue and control unaffected palmar fascia tissue. Dupuytren's tissue also contracts more in the FPCL paradigm. Dicer-substrate RNA-mediated knockdown of EPDR1 results in moderate late stage attenuation of contraction rate in FPCL, implying a role in matrix contraction.
  
  
  CONCLUSIONS
  Our results suggest functional involvement of EPDR1 in the etiology of Dupuytren's Disease.
authors.affiliation: Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, CA, USA.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Staats
authors.affiliation: Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, CA, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Surgery, University of Western Ontario, St Joseph's Health Centre, London, Ontario, Canada; Cell and Molecular Biology Laboratory, Hand and Upper Limb Centre, London, Ontario, Canada.
authors.forename: Bing S
authors.initials: BS
authors.lastname: Gan
authors.affiliation: Department of Surgery, University of Western Ontario, St Joseph's Health Centre, London, Ontario, Canada; Cell and Molecular Biology Laboratory, Hand and Upper Limb Centre, London, Ontario, Canada.
authors.forename: David B
authors.initials: DB
authors.lastname: O'Gorman
authors.affiliation: Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, CA, USA; Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, The Netherlands. Electronic address: Ophoff@ucla.edu.
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004387:Dupuytren Contracture / Q000235:genetics* / Q000378:metabolism*; D005205:Fascia / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009119:Muscle Contraction / Q000235:genetics*; D058628:Myofibroblasts / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide; D061251:Primary Cell Culture; D034622:RNA Interference; D036341:Intercellular Signaling Peptides and Proteins
chemical_list: D003094:Collagen; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C456603:EPDR1 protein, human; D036341:Intercellular Signaling Peptides and Proteins
keywords: Dupuytren’s contracture; Ependymin; FPCL; GWAS; Genetics