Eric R Anderson1, Zhan Ye2, Michael D Caldwell3, James K Burmester4. 1. Surgical Resident, Marshfield Clinic, Marshfield, WI USA eanderson@dshealthcare.com. 2. Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA. 3. Department of General Surgery, Director of Wound Healing Program, Marshfield Clinic, Marshfield, Wisconsin, USA. 4. Clinical Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA.
Abstract
OBJECTIVE: Dupuytren's disease is a progressive fibrosis of the hand that often results in debilitating flexion contractures. Its etiology is not completely understood but likely involves both genetic and environmental factors. A recent study performed in Europe identified DNA variants that associate with Dupuytren's disease. Given the likelihood for genetic variation among populations, we planned to validate the genetic variants identified by this study in a North American population. METHODS: In the Marshfield Clinic's Personalized Medicine Research Project, 296 cases with Dupuytren's disease were identified and matched 3-to-1 to controls without Dupuytren's disease. Clinical data were abstracted from the electronic medical record. The top 12 single nucleotide polymorphisms (SNPs) from the European study were selected and tested in a multiplex assay using the MassArray Analyzer 4 (Sequenom, Inc., San Diego, CA). Differences in allele frequency were determined, and variants with a P value of <0.004 were considered significant. RESULTS: We replicated 5 of the 12 SNPs previously reported to be associated with Dupuytren's disease. CONCLUSION: Our findings support a role for the Wnt signaling pathway in the development of Dupuytren's disease, and suggest that further study of this pathway may result in early diagnosis and non-surgical treatments for Dupuytren's disease.
OBJECTIVE:Dupuytren's disease is a progressive fibrosis of the hand that often results in debilitating flexion contractures. Its etiology is not completely understood but likely involves both genetic and environmental factors. A recent study performed in Europe identified DNA variants that associate with Dupuytren's disease. Given the likelihood for genetic variation among populations, we planned to validate the genetic variants identified by this study in a North American population. METHODS: In the Marshfield Clinic's Personalized Medicine Research Project, 296 cases with Dupuytren's disease were identified and matched 3-to-1 to controls without Dupuytren's disease. Clinical data were abstracted from the electronic medical record. The top 12 single nucleotide polymorphisms (SNPs) from the European study were selected and tested in a multiplex assay using the MassArray Analyzer 4 (Sequenom, Inc., San Diego, CA). Differences in allele frequency were determined, and variants with a P value of <0.004 were considered significant. RESULTS: We replicated 5 of the 12 SNPs previously reported to be associated with Dupuytren's disease. CONCLUSION: Our findings support a role for the Wnt signaling pathway in the development of Dupuytren's disease, and suggest that further study of this pathway may result in early diagnosis and non-surgical treatments for Dupuytren's disease.
Authors: Guido H Dolmans; Paul M Werker; Hans C Hennies; Dominic Furniss; Eleonora A Festen; Lude Franke; Kerstin Becker; Pieter van der Vlies; Bruce H Wolffenbuttel; Sigrid Tinschert; Mohammad R Toliat; Michael Nothnagel; Andre Franke; Norman Klopp; H-Erich Wichmann; Peter Nürnberg; Henk Giele; Roel A Ophoff; Cisca Wijmenga Journal: N Engl J Med Date: 2011-07-06 Impact factor: 91.245
Authors: Katarzyna Ratajczak-Wielgomas; Jerzy Gosk; Jerzy Rabczyński; Katarzyna Augoff; Marzenna Podhorska-Okołów; Andrzej Gamian; Roman Rutowski Journal: Connect Tissue Res Date: 2012-07-24 Impact factor: 3.417
Authors: Jennifer S N Verhoekx; Kate S Beckett; Marcus A Bisson; Duncan A McGrouther; Adriaan O Grobbelaar; Vivek Mudera Journal: J Orthop Res Date: 2012-09-14 Impact factor: 3.494
Authors: Alfiya Akhmetshina; Katrin Palumbo; Clara Dees; Christina Bergmann; Paulius Venalis; Pawel Zerr; Angelika Horn; Trayana Kireva; Christian Beyer; Jochen Zwerina; Holm Schneider; Anika Sadowski; Marc-Oliver Riener; Ormond A MacDougald; Oliver Distler; Georg Schett; Jörg H W Distler Journal: Nat Commun Date: 2012-03-13 Impact factor: 14.919
Authors: Louis Dagneaux; Aaron R Owen; Jacob W Bettencourt; Jonathan D Barlow; Peter C Amadio; Jean P Kocher; Mark E Morrey; Joaquin Sanchez-Sotelo; Daniel J Berry; Andre J van Wijnen; Matthew P Abdel Journal: J Arthroplasty Date: 2020-06-04 Impact factor: 4.757