Polymorphisms in <i><scp>TNC</scp></i> and <i><scp>COL5A1</scp></i> genes are associated with risk of superficial digital flexor tendinopathy in <scp>N</scp>ational <scp>H</scp>unt <scp>T</scp>horoughbred racehorses

Tully, Lindsey; Murphy, A. M.; Smith, R. K. W.; Hulin-Curtis, Sarah; Verheyen, K. L. P.; Price, Joanna S.

doi:10.1111/evj.12134

Cited by 18 publications

(15 citation statements)

References 35 publications

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“…The involvement of these pathways in ACL injuries requires investigation. Similar to the Achilles tendon, variants within the equine TNC and COL5A1 genes are associated with risk of superficial digital flexor tendinopathy in national hunt thoroughbred racehorses 20. Since the same genes have been identified across species, these results strengthen the hypothesis that genetic variants modulate the risk of musculoskeletal soft tissue injuries in humans.…”

Section: Genetic Risk Factors In Other Speciessupporting

confidence: 55%

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Biological variation in musculoskeletal injuries: current knowledge, future research and practical implications

2015

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Evidence from familial and genetic association studies have reported that DNA sequence variants play an important role, together with non-genetic factors, in the aetiology of both exercise-associated and occupational-associated acute and chronic musculoskeletal soft tissue injuries. The associated variants, which have been identified to date, may contribute to the interindividual variation in the structure and, by implication, mechanical properties of the collagen fibril and surrounding matrix within musculoskeletal soft tissues, as well as their response to mechanical loading and other stimuli. Future work should focus on the establishment of multidisciplinary international consortia for the identification of biologically relevant variants involved in modulating injury risk. These consortia will improve the limitations of the published hypothesis-driven genetic association studies, since they will allow resources to be pooled in recruiting large well-characterised cohorts required for whole-genome screening. Finally, clinicians and coaches need to be aware that many direct-to-consumer companies are currently marketing genetic tests directly to athletes without it being requested by an appropriately qualified healthcare professional, and without interpretation alongside other clinical indicators or lifestyle factors. These specific genetic tests are premature and are not necessarily required to evaluate susceptibility to musculoskeletal soft tissue injury. Current practice should rather consider susceptibility through known risk factors such as a positive family history of a specific injury, a history of other tendon and/or ligament injuries and participation in activities associated with the specific musculoskeletal injuries. Potential susceptible athletes may then be individually managed to reduce their risk profile.

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Section: Genetic Risk Factors In Other Speciessupporting

confidence: 55%

“…1),2–8 Achilles tendon injuries (reviewed in refs. 9 and 10),4 11 12 lateral epicondylitis,13 rotator cuff injuries14–16 and carpal tunnel syndrome17–19 in humans, as well as, equine superficial digital flexor tendinopathy20 and canine cranial cruciate ligament rupture (CCLR) 21 22…”

Section: Introductionmentioning

confidence: 99%

Biological variation in musculoskeletal injuries: current knowledge, future research and practical implications

2015

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“…Additional risk factors for tendon injury include high levels of repetitive loading (8), genetic factors (9, 10), and chronic inflammation (11). However, the cellular and molecular mechanisms underpinning this increased risk in tendons are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis Reveals Age-related Changes in Tendon Matrix Composition, with Age- and Injury-specific Matrix Fragmentation

Peffers

Thorpe

Collins

et al. 2014

Journal of Biological Chemistry

111

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Background: Alterations in tendon matrix composition with aging and injury are poorly understood.Results: Aging and injury resulted in distinct protein profiles, with age-specific peptide fragmentation in injury.Conclusion: Identification of protein cleavages associated with aging and injury suggest impaired maintenance and repair in aged tendon.Significance: Novel peptide fragments identified are potential biomarkers of tendon injury and age-related degeneration.

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“…While SNP variants of matrix proteins in DSLD-Pasos have not been reported, recent analysis of 270 racehorses with superficial digital flexor tendinopathy (SDFT) has suggested (odds ratio, 2.77) an association with a G >A substitution in the COL5A1 gene [13], which, along with variants in other genes, such COL27A1 , CASP8 , MMP3 , FBN2 , TIMP2 , has been implicated in matrix changes in various human tendinopathies [14]. A genetic predisposition to defective matrix organization in human tendinopathy is also supported by a recent bioinformatics analysis [15], which identified four strong candidate risk genes ( COL11A2 , ELN , ITGB3 , LOX ), each of which functions in the controlled turnover of fibrous tissue matrix.…”

Section: Introductionmentioning

confidence: 99%

Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts

et al. 2016

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Equine degenerative suspensory ligament desmitis (DSLD) in Peruvian Paso horses typically presents at 7–15 years and is characterized by lameness, focal disorganization of collagen fibrils, and chondroid deposition in the body of the ligament. With the aim of developing a test for disease risk (that can be used to screen horses before breeding) we have quantified the expression of 76 TGFβ-signaling target genes in adipose-derived stromal fibroblasts (ADSCs) from six DSLD-affected and five unaffected Paso horses. Remarkably, 35 of the genes showed lower expression (p<0.05) in cells from DSLD-affected animals and this differential was largely eliminated by addition of exogenous TGFβ1. Moreover, TGFβ1-mediated effects on expression were prevented by the TGFβR1/2 inhibitor LY2109761, showing that the signaling was via a TGFβR1/2 complex. The genes affected by the pathology indicate that it is associated with a generalized metabolic disturbance, since some of those most markedly altered in DSLD cells (ATF3, MAPK14, ACVRL1 (ALK1), SMAD6, FOS, CREBBP, NFKBIA, and TGFBR2) represent master-regulators in a wide range of cellular metabolic responses.

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Polymorphisms in TNC and COL5A1 genes are associated with risk of superficial digital flexor tendinopathy in National Hunt Thoroughbred racehorses

Abstract: Results suggest that sequence variants in TNC and COL5A1 genes are associated with SDF tendinopathy in TB racehorses. In future genetic markers may be used to identify horses at risk of SDF tendinopathy.

Cited by 18 publications

References 35 publications

Biological variation in musculoskeletal injuries: current knowledge, future research and practical implications

Biological variation in musculoskeletal injuries: current knowledge, future research and practical implications

Proteomic Analysis Reveals Age-related Changes in Tendon Matrix Composition, with Age- and Injury-specific Matrix Fragmentation

Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts

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