Dataset Information

Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy.

ABSTRACT: Achilles tendinopathy or rupture and anterior cruciate ligament (ACL) rupture are substantial injuries affecting athletes, associated with delayed recovery or inability to return to competition. To identify genetic markers that might be used to predict risk for these injuries, we performed genome-wide association screens for these injuries using data from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort consisting of 102,979 individuals. We did not find any single nucleotide polymorphisms (SNPs) associated with either of these injuries with a p-value that was genome-wide significant (p<5x10-8). We found, however, four and three polymorphisms with p-values that were borderline significant (p<10-6) for Achilles tendon injury and ACL rupture, respectively. We then tested SNPs previously reported to be associated with either Achilles tendon injury or ACL rupture. None showed an association in our cohort with a false discovery rate of less than 5%. We obtained, however, moderate to weak evidence for replication in one case; specifically, rs4919510 in MIR608 had a p-value of 5.1x10-3 for association with Achilles tendon injury, corresponding to a 7% chance of false replication. Finally, we tested 2855 SNPs in 90 candidate genes for musculoskeletal injury, but did not find any that showed a significant association below a false discovery rate of 5%. We provide data containing summary statistics for the entire genome, which will be useful for future genetic studies on these injuries.

SUBMITTER: Kim SK

PROVIDER: S-EPMC5373512 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy.

Kim Stuart K SK Roos Thomas R TR Roos Andrew K AK Kleimeyer John P JP Ahmed Marwa A MA Goodlin Gabrielle T GT Fredericson Michael M Ioannidis John P A JP Avins Andrew L AL Dragoo Jason L JL

PloS one 20170330 3

Achilles tendinopathy or rupture and anterior cruciate ligament (ACL) rupture are substantial injuries affecting athletes, associated with delayed recovery or inability to return to competition. To identify genetic markers that might be used to predict risk for these injuries, we performed genome-wide association screens for these injuries using data from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort consisting of 102,979 individuals. We did not find any single nucleo ...[more]

PMID: 28358823

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Project description:BackgroundFamilial hypercholesterolemia is a genetic condition characterized by life-long elevations of plasma low-density lipoprotein cholesterol. In addition to life-threatening cardiovascular complications, intratendinous cholesterol deposits (xanthomas) can lead to pain and tendon thickening, particularly in the Achilles. Clinical detection of xanthomas currently relies upon visual assessment and palpation, or ultrasound-based measures of tendon thickening or echotexture. Misdiagnosis of xanthoma can delay the commencement of potentially life-saving lipid-lowering therapy. Our primary purpose was to determine whether analysis of separated fat and water magnetic resonance images may be able to differentiate between xanthomatic and nonxanthomatic Achilles tendons through quantification of intratendinous fat content. The main hypothesis was that Achilles tendon xanthomas will demonstrate greater lipid content than Achilles tendinopathy or healthy control tendons.MethodsBilateral MRI scans of Achilles tendons from 30 participants (n = 10 Achilles tendon xanthoma, n = 10 Achilles overuse tendinopathy, n = 10 healthy controls) were analyzed for total lipid content using the Dixon method of fat and water signal separation. Secondary outcome measures included tendon water content, as well as ultrasound characterization of tendon tissue organization and thickness.ResultsFat content was greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p < 0.0001). Water content was also greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p = 0.0002). Ultrasound tissue characterization revealed worse tissue organization in Achilles tendon xanthoma tendons compared to Achilles tendinopathy (p < 0.05) but demonstrated largely overlapping distributions. Achilles tendon xanthoma tendons were, on average, significantly thicker than the tendons of the other two groups (p < 0.01 and p < 0.001, respectively).ConclusionMRI-derived measures of Achilles tendon fat content may be able to distinguish xanthomas from control and tendinopathic tissue. Dixon method MRI warrants further evaluation in an adequately powered study to develop and test clinically relevant diagnostic thresholds.

Project description:OBJECTIVES:The objective of the current cross-sectional study was to examine Achilles tendon transverse stiffness in a group of recreational runners with Achilles tendinopathy, in comparison to an asymptomatic group of runners with similar training history. We also aimed to determine the between-week intra-individual reliability of this measurement technique. DESIGN:Cross-sectional cohort study. METHODS:A hand-held dynamometer was used to assess the transverse stiffness of the Achilles tendon (AT) in twenty-five recreational runners. In ten people with midportion Achilles tendinopathy (5 men, 5 women), measurements were taken directly over the most symptomatic location. In 15 people who were free of AT symptoms (7 men, 8 women), measurements were taken at an equivalent location on the tendon. Participants returned after one week to determine measurement reliability (intra-class correlation coefficient/ICC and minimum detectable change/MDC95). We also collected information about people's tendon loading activities, tendon thickness (ultrasound mesaurement), and symptoms (Victorian Institute of Sports Assessment-Achilles / VISA-A score). RESULTS:The AT transverse stiffness was lower in people with Achilles tendinopathy (777 N/m ± 86) compared to those who were asymptomatic (873 N/m ± 72) (p < 0.05). AT transverse stiffness was negatively correlated with age and tendon thickness, and positively correlated with VISA-A score and waist circumference. Reliability was good, with ICC of 0.81 in people with tendinopathy and 0.80 in healthy controls, and an MDC95 of 118 and 87N/m in these two respective groups. CONCLUSIONS:Transverse Achilles tendon stiffness can be reliably measured in people with midportion Achilles tendinopathy, and appears to be lower in people who are older, more symptomatic, and with more extensive tendon thickening. The potential clinical utility of monitoring tendon stiffness in the management of tendon injuries merits further study.

Project description:PurposeTo evaluate functional outcomes, return to work, and reoperations associated with lower trapezius tendon transfer (LTT) for irreparable rotator cuff tears.MethodsThis is a retrospective study performed by a single surgeon with minimum 1-year follow-up. LTT was performed using an open (n = 9; 60%) or arthroscopically assisted (n = 6, 40%) technique. Outcomes included failure rate, range of motion, satisfaction, return to work, and pre- and postoperative functional scores, as well as American Shoulder and Elbow Surgeons score, Single Assessment Numeric Evaluation, and the Simple Shoulder Test.ResultsFifteen patients were included. LTT was performed using an open or arthroscopically assisted technique. Mean age was 52 (range 31-62 years), 13 (92.9%) were manual laborers, and 9 (60%) had a worker's compensation claim. Three patients (20%) underwent conversion to reverse shoulder arthroplasty. Of the remaining 12 patients, there were significant improvements in American Shoulder and Elbow Surgeons, Single Assessment Numeric Evaluation, and Simple Shoulder Test at 24.1 ± 9.6 (range 12-38.5) months. Active forward elevation, abduction, and external rotation were all significantly improved. Postoperative satisfaction ratings indicated 67% of the revision-free cohort was "very satisfied" and 33% was "somewhat satisfied" with their outcome. Seven (50%) returned to full duty, 4 (28.6%) returned to modified duty, and 3 (21.4%) were unable to return to work. Two patients (open techniques) underwent a superficial wound debridement for seroma and wound breakdown.ConclusionsLTT results in successful clinical outcomes with a high rate of return to work in a challenging patient population. However, only 67% of patients rated themselves as "very satisfied," and 20% of patients were revised to reverse shoulder arthroplasty before 1 year. Limited preoperative active forward elevation (<90°) appears to predict poor functional results and risk for reoperation.Level of evidenceLevel IV, therapeutic case series.

Project description:ObjectiveTo identify latent subgroups among patients with Achilles tendinopathy, describe patient characteristics and clinical attributes that defined each subgroup, and develop a clinical classification model for subgroup membership.DesignCross-sectional study.MethodsOne hundred forty-five participants (men, n = 73; mean ± SD age, 51 ± 14 years) with clinically diagnosed Achilles tendinopathy completed a baseline evaluation, including demographics and medical history, patient-reported outcome measures, a clinical exam, tendon structure measures via ultrasound imaging and continuous shear-wave elastography, and a functional test battery. Subgroups were identified using mixture modeling. We compared the subgroups using a 1-way analysis-of-variance or chi-square test and the Tukey post hoc test to identify defining attributes. We developed a clinical classification model using logistic regression and receiver operating characteristic curves.ResultsThree latent subgroups were identified and named by their distinctive patient characteristics and clinical attributes. The activity-dominant subgroup (n = 67), on average, had the highest physical activity level, function, and quality of life; reported mild symptoms; and was the youngest. The psychosocial-dominant subgroup (n = 56), on average, had the worst symptoms, impaired function, heightened psychological factors, the poorest quality of life, minimal tendon structural alterations, and was obese and predominantly female. The structure-dominant subgroup (n = 22), on average, had the most tendon structural alterations, severe functional deficits, moderate symptoms and psychological factors, reduced quality of life, and was the oldest, obese, and predominantly male. The clinical classification model correctly classified 85% (123/145) of participants.ConclusionThree Achilles tendinopathy subgroups (activity dominant, psychosocial dominant, and structure dominant) differed in patient characteristics and clinical attributes. J Orthop Sports Phys Ther 2021;51(9):440-448. Epub 1 Jun 2021. doi:10.2519/jospt.2021.10271.

Project description:BackgroundAssuming that the mechanisms inducing adaptation in healthy tendons yield similar responses in tendinopathic tendons, we hypothesized that a high-loading exercise protocol that increases tendon stiffness and cross-sectional area in male healthy Achilles tendons may also induce comparable beneficial adaptations in male tendinopathic Achilles tendons in addition to improving pain and function.ObjectivesWe investigated the effectiveness of high-loading exercise in Achilles tendinopathy in terms of inducing mechanical (tendon stiffness, maximum strain), material (Young's modulus), morphological (tendon cross-sectional area (CSA)), maximum voluntary isometric plantar flexor strength (MVC) as well as clinical adaptations (Victorian Institute of Sports Assessment-Achilles (VISA-A) score and pain (numerical rating scale (NRS))) as the primary outcomes. As secondary outcomes, drop (DJ) and counter-movement jump (CMJ) height and intratendinous vascularity were assessed.MethodsWe conducted a controlled clinical trial with a 3-month intervention phase. Eligibility criteria were assessed by researchers and medical doctors. Inclusion criteria were male sex, aged between 20 and 55 years, chronic Achilles tendinopathy confirmed by a medical doctor via ultrasound-assisted assessment, and a severity level of less than 80 points on the VISA-A score. Thirty-nine patients were assigned by sequential allocation to one of three parallel arms: a high-loading intervention (training at ~ 90% of the MVC) (n = 15), eccentric exercise (according to the Alfredson protocol) as the standard therapy (n = 15) and passive therapy (n = 14). Parameters were assessed pre- and-post-intervention. Data analysis was blinded.ResultsPrimary outcomes: Plantar flexor MVC, tendon stiffness, mean CSA and maximum tendon strain improved only in the high-loading intervention group by 7.2 ± 9.9% (p = 0.045), 20.1 ± 20.5% (p = 0.049), 8.98 ± 5.8% (p < 0.001) and -12.4 ± 10.3% (p = 0.001), respectively. Stiffness decreased in the passive therapy group (-7.7 ± 21.2%; p = 0.042). There was no change in Young's modulus in either group (p > 0.05). The VISA-A score increased in all groups on average by 19.8 ± 15.3 points (p < 0.001), while pain (NRS) dropped by -0.55 ± 0.9 points (p < 0.001).Secondary outcomesCMJ height decreased for all groups (-0.63 ± 4.07 cm; p = 0.005). There was no change in DJ height and vascularity (p > 0.05) in either group.ConclusionDespite an overall clinical improvement, it was exclusively the high-loading intervention that induced significant mechanical and morphological adaptations of the plantar flexor muscle-tendon unit. This might contribute to protecting the tendon from strain-induced injury. Thus, we recommend the high-loading intervention as an effective (alternative) therapeutic protocol in Achilles tendinopathy rehabilitation management in males.Clinical trials registration numberNCT02732782.

Dataset Information

Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy.

Publications

Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy.

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