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Genetic component to achilles tendon pathology

Discussion in 'Biomechanics, Sports and Foot orthoses' started by admin, Mar 24, 2005.

  1. admin

    admin Administrator Staff Member


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    The COL5A1 gene and Achilles tendon pathology
    Scandinavian Journal of Medicine & Science in Sports
    G. G. Mokone, M. P. Schwellnus, T. D. Noakes, M. Collins

     
    Last edited by a moderator: Nov 20, 2012
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    More on genetics and achilles tendon pathology

    Increased expression of aggrecan and biglycan mRNA in Achilles tendinopathy
    Rheumatology 2006 45(3):291-294;
     
    Last edited: Nov 20, 2012
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    From the ACSM Mtg:
    Structural And Physiological Changes In Chronically overused Achilles tendons
    Henning Langberg, Jessica Pingel, Ulrich Fredberg, Klaus Qvortrup, Jytte Overgaard, Michael Kjaer
     
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    MOLECULAR GENETICS AN IMPORTANT TOOL IN ELUCIDATING THE MOLECULAR MECHANISMS UNDERLYING TENDINOPATHIES
    M. Collins
    2nd International Scientific Tendinopathy Symposium; Vancouver Sept 27-29 2012
     
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    AN ASSOCIATION BETWEEN COMPONENTS OF THE APOPTOSIS PATHWAY AND THE GENETIC PREDISPOSITION TO ACHILLES TENDINOPATHY
    E Nell, L van der Merwe, J Cook, CJ Handley, M Collins and AV September
    2nd International Scientific Tendinopathy Symposium; Vancouver Sept 27-29 2012
     
    Last edited: Nov 20, 2012
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    Analysis of hereditary and medical risk factors in Achilles tendinopathy and Achilles tendon ruptures: a matched pair analysis
    Robert Kraemer, Waldemar Wuerfel, Johan Lorenzen, Marc Busche, Peter M. Vogt, Karsten Knobloch
    Archives of Orthopaedic and Trauma Surgery June 2012, Volume 132, Issue 6, pp 847-853
     
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    Investigation of variants within the COL27A1 and TNC genes and Achilles tendinopathy in two populations
    Colleen J. Saunders et al
    Journal of Orthopaedic Research (in Press)
     
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    Polymorphisms within the COL5A1 3′-UTR That Alters mRNA Structure and the MIR608 Gene are Associated with Achilles Tendinopathy
    Yoonus Abrahams, Mary-Jessica Laguette, Sharon Prince, Malcolm Collins
    Annals of Human Genetics (online first)
     
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    Pathology of the tendo Achillis; Do our genes contribute?
    W. J. Ribbans, M. Collins
    Bone Joint J March 2013 vol. 95-B no. 3 305-313
     
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    The Peripheral Neuronal Phenotype is Important in the Pathogenesis of Painful Human Tendinopathy: A Systematic Review
    Benjamin John Floyd Dean MRCS (Ed),Sarah L. Franklin PhD, Andrew Jonathan Carr FRCS, FMedSci
    Clinical Orthopaedics and Related Research®; April 2013
     
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    Association of type XI collagen genes with chronic Achilles tendinopathy in independent populations from South Africa and Australia
    Melanie Hay, Jon Patricios, Robert Collins, Andy Branfield, Jill Cook, Christopher J Handley, Alison V September, Michael Posthumus, Malcolm Collins
    Br J Sports Med doi:10.1136/bjsports-2013-092379
     
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    IMPORTANCE OF GENETIC VARIANTS AND ETHNICITY IN NON-CONTACT MUSCULOSKELETAL SOFT TISSUE INJURIES
    Pruna Ricard, Artells Rosa, Ribas Jordi, Montoro Bruno, Monzo Mariano
    Br J Sports Med 2013;47:e3
     
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    The Peripheral Neuronal Phenotype is Important in the Pathogenesis of Painful Human Tendinopathy: A Systematic Review.
    AuthorsDean BJ, et al.
    Clin Orthop Relat Res. 2013 Apr 23.
     
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    BMP4 and FGF3 haplotypes increase the risk of tendinopathy in volleyball athletes
    José Inácio Salles et al
    Journal of Science and Medicine in Sport; Available online 1 March 2014
     
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    The COL5A1 Gene and Risk of Achilles Tendon Pathology in a British Cohort
    Louis El Khoury, Michael Posthumus, Malcolm Collins, William Ribbans, Stuart Raleigh
    Br J Sports Med 2014;48:A54 doi:10.1136/bjsports-2014-094114.81
     
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    Extracellular matrix proteins interact with cell-signalling pathways in modifying risk of Achilles tendinopathy
    Colleen J. Saunders, Lize van der Merwe, Jill Cook, Christopher J. Handley, Malcolm Collins and Alison V. September
    Journal of Orthopaedic Research; Accepted Article
     
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    Variation within three apoptosis associated genes as potential risk factors for Achilles tendinopathy in a British based case–control cohort
    Rebecca Rickby, Louis El Khoury, William J. Ribbans, Stuart M. Raleigh,
    Gene; Available online 5 June 2015
     
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    THE COL5A1 3′-UTR AND CHRONIC ACHILLES TENDINOPATHY: A FUNCTIONAL STUDY
    M-J Laguette, S Prince and M Collins
    Bone Joint J 2015 vol. 97-B no. SUPP 11 32
     
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    GENETIC RISK FACTORS FOR MID-PORTION ACHILLES TENDINOPATHY: A SYSTEMATIC REVIEW
    AA Chauhan, D Morrissey, PR Jones, M Angioi, B Kumar, H Langberg, N Maffulli and P Malliaras
    Bone Joint J 2015 vol. 97-B no. SUPP 11 32
     
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    Characterisation of the 3'-UTR of the COL5A1 gene: implication for musculoskeletal soft tissue injuries
    Laguette, Mary-Jessica Nancy
    University of Cape Town Thesis, 2015
     
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    MMP3 and TIMP2 gene variants as predisposing factors for Achilles tendon pathologies: Attempted replication study in a British case-control cohort
    Louis El Khoury et al
    Meta Gene; 30 March 2016
     
  22. Dananberg

    Dananberg Active Member

    While this is 100% anecdotal, one of my son's closest friends ruptured his L Achilles tendon. His father had the same injury at the same age, and within one month of the actual date of injury. Always spooked me a bit!
     
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    The MMP3 gene in musculoskeletal soft tissue injury risk profiling: A study in two independent sample groups
    A. Gibbon et al
    Journal of Sports Sciences; in press
     
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    PUBLIC RELEASE: 13-JUL-2016
    Tendon, heal thyself!
    New TSRI study reveals gene crucial in keeping tendons healthy
     
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    Human Genetic Variation, Sport and Exercise Medicine, and Achilles Tendinopathy: Role for Angiogenesis-Associated Genes
    Rahim Masouda, El Khoury Louis Y., Raleigh Stuart M., Ribbans William J., Posthumus Michael, Collins Malcolm, and September Alison V..
    OMICS: A Journal of Integrative Biology. September 2016, 20(9): 520-527.
     
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    Vascular Endothelial Growth Factor Receptor-2 Polymorphisms Have Protective Effect against the Development of Tendinopathy in Volleyball Athletes
    José Inácio Salles, Maria Eugenia Leite Duarte, João Matheus Guimarães, Lucas Rafael Lopes, Jessica Vilarinho Cardoso, Diego Pinheiro Aguiar, João Olyntho Machado Neto, Daniel Escorsim Machado, Jamila Alessandra Perini
    PLoS ONE 11(12): e0167717. doi:10.1371/journal.pone.0167717
    .
     
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    Genetic Factors in Tendon Injury: A Systematic Review of the Literature
    Natalie H. Vaughn, MD, Hayk Stepanyan, MD, Robert A. Gallo, MD, ...
    Orthopaedic Journal of Sports Medicine August 23, 2017
     
  28. Dananberg

    Dananberg Active Member

    A very close friend of my son ruptured his A-tendon playing basketball at age 29. It was on the same side and within a month in age of his father's A-tendon rupture 27 years earlier. As Yogi Berra said, it's too coincidental to be a coincidence!
     
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    Defining the molecular signatures of Achilles tendinopathy and anterior cruciate ligament ruptures: A whole-exome sequencing approach.
    Gibbon A et al
    PLoS One. 2018 Oct 25;13(10):e0205860.
     
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    Association of COL5A1 gene polymorphisms and risk of tendon-ligament injuries among Caucasians: a meta-analysis
    Noel PabalanPhuntila TharabenjasinSuphawadee PhababphaHamdi Jarjanazi
    Sports Medicine; December 2018
     
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    15-epi-LXA4 and MaR1 counter inflammation in stromal cells from patients with Achilles tendinopathy and rupture
    Stephanie G. Dakin, Romain A. Colas, Julia Newton, Stephen Gwilym, Natasha Jones, Hamish A. B. Reid, Simon Wood, Louise Appleton, Kim Wheway,
    Source
     
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    Expression of TGF-β1 and VEGF in patients with Achilles tendon rupture and the clinical efficacy.
    Cui J et al
    Exp Ther Med. 2019 Nov;18(5):3502-3508
     
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    Variability within the human iNOS gene and Achilles tendon injuries: Evidence for a heterozygous advantage effect
    Charlotte Brookes et al
    Article in Press; JSAMS
     
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    Relationship of common variants in MPP7, TIMP2 and CASP8 genes with the risk of chronic achilles tendinopathy
    Xin Kang, Bin Tian, Liang Zhang, Zhaogang Ge, Yang Zhao & Yingang Zhang
    Scientific Reports volume 9, Article number: 17627 (2019)
     
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    Identification of Three Loci Associated with Achilles Tendon Injury Risk from a Genome-wide Association Study
    Kim, Stuart K et al
    Medicine & Science in Sports & Exercise: February 18, 2021
     
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    Gait analysis combined with the expression of TGF-β1, TGF-β3 and CREB during Achilles tendon healing in rat
    Li-MingWu et al
    Chinese Journal of Traumatology; 12 October 2021
     
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    Association between matrix metalloproteinase-3 gene polymorphisms and tendon-ligament injuries: evidence from a meta-analysis
    Rui Guo, Aihaiti Aizezi, Yong Fan, Zhe Ji, Wenzong Li, Yongxian Li, Zhigang Wang & Kai Ning
    BMC Sports Science, Medicine and Rehabilitation volume 14, Article number: 26 (2022)
     
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    Press Release:
    Move over muscles, it’s time for tendons to be in the spotlight
    Tendon-specific gain-of-function mutation of Piezo1 enhances jumping power


    Researchers at Tokyo Medical and Dental University (TMDU),Scripps Research, and others found that tendons, not muscles, are the crucial site where increased expression of a mechanosensitive ion channels translates to better running and jumping capabilities



    Tokyo, Japan—A gene (PIEZO1) for ion channels that govern cellular responses to mechanical stimuli may be a potential target for therapies for musculoskeletal disorders. Cells that are activated by mechanical stress (i.e., mechanosensitive) allow, for example, the sensation of touch at the fingertips. In bones, muscles, and tendons, mechanosensitive cells also play an important role—by initiating the production or breakdown of tissue in response to physical demands. New findings show that a significant biomechanical advantage is imparted by increased mechanosensitivity in tendons.

    In a comprehensive study published this month in Science Translational Medicine, researchers at TMDU, Scripps Research, and others found that a genetic variant (R2482H Piezo1) in mice, which is analogous to one (E756del PIEZO1) in humans, produced cellular changes in tendons that translated to altered tissue properties and physical characteristics, which in turn translated to better athletic ability.

    Both the human genetic variant and the mouse genetic variant were known to impart resistance to malaria (by altering the shape of red blood cells) and were associated with better tendon properties in mice and better jumping ability in humans. However, the link between genetic expression and physical performance was unclear.

    The research team compared four groups of mice: wild-type mice (with no modifications to gene expression) and mice with tendon-specific, muscle-specific, or whole-body expression of the genetic variant. “Tendons were able to stretch more easily and store larger amounts of energy, which allowed for greater flexion and greater instantaneous power produced by the ankle, whether alterations were innate or introduced after mice matured,” explains senior author Hiroshi Asahara. “Muscle-specific alterations, however, did not result in improved physical performance.”

    High expression of the calcium-ion channel mechanoreceptor coincided with high expression of two transcription factors, found only in tendon cells, that regulate genes for collagen and proteoglycan production.

    Lead author Ryo Nakamichi explains, “Given these findings, we looked at tendon structure and composition more closely. Increased mechanosensitivity, from either tendon-specific or whole-body alterations, resulted in wider tendons composed of collagen fibrils with larger diameters.”

    To put the findings from mice into human context, the research team replicated the effect of PIEZO1 activation on expression of the same two transcription factors in human tendon and, in addition, compared the frequency of the E756del PIEZO1 genetic variant in elite sprinters with that of nonathletes in Jamaica (because the variant occurs in a larger proportion in populations of African descent). The frequency of E756del PIEZO1 was significantly higher in the sprinters.

    This finding that the specific variant of PIEZO1 gene can potentiate physical activity may eventually allow for new treatments for individuals with tendinopathy or other tendon-related disorders to be developed.
     
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    Genetic Variants within NOGGIN, COL1A1, COL5A1, and IGF2 are Associated with Musculoskeletal Injuries in Elite Male Australian Football League Players: A Preliminary Study
    Ysabel Jacob, Ryan S. Anderton, Jodie L. Cochrane Wilkie, Brent Rogalski, Simon M. Laws, Anthony Jones, Tania Spiteri, Dana Hince & Nicolas H. Hart
    Sports Medicine - Open volume 8, Article number: 126 (2022)
     
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    Genetic Variants within NOGGIN, COL1A1, COL5A1, and IGF2 are Associated with Musculoskeletal Injuries in Elite Male Australian Football League Players: A Preliminary Study
    Ysabel Jacob, Ryan S. Anderton, Jodie L. Cochrane Wilkie, Brent Rogalski, Simon M. Laws, Anthony Jones, Tania Spiteri, Dana Hince & Nicolas H. Hart
    Sports Medicine - Open volume 8, Article number: 126 (2022)
     
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