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Malcolm Collins
University of Cape Town, Human Biology, Faculty Member
- Prof Malcolm Collins is head of the University of Cape Town’s (UCT) Division of Physiological Sciences in South Afric... moreProf Malcolm Collins is head of the University of Cape Town’s (UCT) Division of Physiological Sciences in South Africa. Prof Collins’ doctoral and post-doctoral work, at UCT and the University of Washington in Seattle, respectively, in extracellular matrix biology stimulated his current research focus on elucidating the molecular mechanisms causing common exercise- and occupation-associated tendon and ligament injuries. He has developed a very productive internationally recognized research team which has published over 150 papers and book chapters. He is a Fellow of the European College of Sport Science and a Member of the Academy of Science of South Africa.edit
Measuring the DNA telomere length of skeletal muscle in experienced endurance runners may contribute to our understanding of the effects of chronic exposure to endurance exercise on skeletal muscle. This study compared the minimum... more
Measuring the DNA telomere length of skeletal muscle in experienced endurance runners may contribute to our understanding of the effects of chronic exposure to endurance exercise on skeletal muscle. This study compared the minimum terminal restriction fragment (TRF) length in the vastus lateralis muscle of 18 experienced endurance runners (mean age: 42 +/- 7 years) to those of 19 sedentary individuals (mean age: 39 +/- 10 years). The runners had covered almost 50,000 km in training and racing over 15 years. Minimum TRF lengths measured in the muscle of both groups were similar (P = 0.805) and within the normal range. Minimum TRF length in the runners, however, was inversely related to their years spent running (r = -0.63, P = 0.007) and hours spent training (r = -0.52, P = 0.035). Therefore, since exposure to endurance running may influence minimum TRF length, and by implication, the proliferative potential of the satellite cells, chronic endurance running may be seen as a stressor to skeletal muscle.
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The aim of this study was to examine the interaction between aging and 10 years of racing in endurance runners. Race-time data from 194 runners who had completed 10 consecutive 56-km ultramarathons were obtained. The runners were either... more
The aim of this study was to examine the interaction between aging and 10 years of racing in endurance runners. Race-time data from 194 runners who had completed 10 consecutive 56-km ultramarathons were obtained. The runners were either 20.5 ± 0.7, 30.0 ± 1.0, 39.9 ± 0.9, or 49.4 ± 1.0 years old at their first race. Each runner’s race speed was determined for each race over the 10 years. Data were analyzed using repeated-measures ANOVA, one-way ANOVA, and independent t tests and showed that performance improved and declined at greater rates for younger runners; younger runners had a greater capacity for improvement than older runners; ≈4 years were required to reach peak racing speed, regardless of age; it was not possible to compete at peak speed for more than a few years; and the combined effects of 10 years of aging and racing neither improve nor worsen net performance. In conclusion, these data suggest that although these runners showed similar patterns of change in race speed o...
Research Interests: Running, Medicine, Humans, Female, Male, and 5 moreAged, Middle Aged, Adult, Age Factors, and Physical Endurance
This study analyzed the effect of caffeine ingestion on performance during a repeated-measures, 100-km, laboratory cycling time trial that included bouts of 1- and 4-km high intensity epochs (HIE). Eight highly trained cyclists... more
This study analyzed the effect of caffeine ingestion on performance during a repeated-measures, 100-km, laboratory cycling time trial that included bouts of 1- and 4-km high intensity epochs (HIE). Eight highly trained cyclists participated in 3 separate trials' placebo ingestion before exercise with a placebo carbohydrate solution and placebo tablets during exercise (Pl), or placebo ingestion before exercise with a 7% carbohydrate drink and placebo tablets during exercise (Cho), or caffeine tablet ingestion before and during exercise with 7% carbohydrate (Caf). Placebo (twice) or 6 mg.kg(-1) caffeine was ingested 60 min prior to starting 1 of the 3 cycling trials, during which subjects ingested either additional placebos or a caffeine maintenance dose of 0.33 mg.kg(-1) every 15 min to trial completion. The 100-km time trial consisted of five 1-km HIE after 10, 32, 52, 72, and 99 km, as well as four 4-km HIE after 20, 40, 60, and 80 km. Subjects were instructed to complete the t...
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Cartilage oligomeric matrix protein is a structural protein of the extracellular matrix, while thrombospondin-2 is a matricellular protein involved in cell–matrix interactions. Recent studies have shown that genetic variation is a... more
Cartilage oligomeric matrix protein is a structural protein of the extracellular matrix, while thrombospondin-2 is a matricellular protein involved in cell–matrix interactions. Recent studies have shown that genetic variation is a significant risk factor for Achilles tendinopathy, and the genes encoding cartilage oligomeric matrix protein (COMP) and thrombospondin-2 (THBS2) were identified as good candidate genes for association with Achilles tendinopathy. This study aimed to test the association of sequence variants within these candidate genes with the risk of Achilles tendinopathy in participants from South Africa (SA) and Australia (AUS). Three-hundred and forty (133 SA; 207 AUS) control participants with no history of Achilles tendinopathy and 178 (94 SA; 84 AUS) participants clinically diagnosed with Achilles tendinopathy were genotyped for five single nucleotide polymorphisms within the COMP and THBS2 genes in this case-control study. There was no difference in genotype distr...
Research Interests: Australia, Biology, Molecular Genetics, Medicine, Musculoskeletal Injury Prevention, and 15 moreSouth Africa, Humans, Female, Male, Genetic Association Studies, Tendinopathy, Risk factors, Adult, Sports Sciences, Curriculum and Pedagogy, Soft Tissue Injuries, Body Weight, Risk Factors, Case Control Studies, and Gene frequency
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This study compared differences in maximal strength and aerobic capacity and symptoms of fatigue and depression in athletes with acquired training intolerance (ATI) and control athletes (CON) matched for age and current training volume... more
This study compared differences in maximal strength and aerobic capacity and symptoms of fatigue and depression in athletes with acquired training intolerance (ATI) and control athletes (CON) matched for age and current training volume who did not have symptoms of excessive or chronic fatigue associated with their sporting activity. University of Cape Town, Sports Science Institute of South Africa. Twenty ATI and 10 CON athletes participated in the trial. Although the ATI athletes reported symptoms of excessive fatigue during exercise, or symptoms of fatigue that occurred at rest and during activities of daily living, they did not fulfill the criteria for a diagnosis of chronic fatigue syndrome. A training and comprehensive medical history was recorded from all subjects. The Beck Depression Inventory Short Form (BDI-SF) was used to assess levels of depression in both ATI and control subjects. Maximal force output during a 5-second isometric voluntary knee extensor muscle contraction, and maximal aerobic capacity (VO2max), maximal heart rate (HRmax), and maximal blood lactate concentrations during a treadmill running test were measured in all subjects. There were no differences in maximal isometric force output, peak treadmill running speed, VO2max, HRmax, or blood lactate concentration at rest or after maximal exercise testing between the ATI and CON athletes. However, the BDI-SF scores were higher in the ATI (7.7 +/- 6.6 arbitrary units) than in the CON athletes (1.7 +/- 1.5 arbitrary units; (P = 0.0052). These findings suggest that the symptoms of excessive fatigue and acquired training intolerance described by these ATI athletes do not affect their maximal isometric and maximal aerobic capacity, and may be associated with psychologic depression in these athletes.
Research Interests: Depression, Fatigue, Medicine, Sports, Humans, and 6 moreChronic Disease, Female, Male, Adult, Oxygen Consumption, and Exercise Tolerance
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To date, more than 18 genomic intervals, which underpin the complex myriad of extracellular matrix interactions of tendons, have been implicated in risk models for tendinopathy. It is these relationships that most likely regulate the... more
To date, more than 18 genomic intervals, which underpin the complex myriad of extracellular matrix interactions of tendons, have been implicated in risk models for tendinopathy. It is these relationships that most likely regulate the tissue's response to loading and unloading, thereby dictating the overall capacity of tendons and influencing injury susceptibility. The evidence suggesting a genetic contribution to the susceptibility of sustaining a tendon injury is growing. However, only a few of the loci have been repeated in independent studies, of which some have included a range of musculoskeletal soft tissues injuries. Case-control study designs can be effective in capturing risk, provided that the cases and controls are equally well-defined and carefully considered. The genome consists of 3.6 × 10(9) sequences and therefore we realise that we are far from decoding all the genomic signatures. We are indeed fortunate to be living in such exciting times where high-throughput technologies are at our disposal. Through collaboration, our chances of harnessing these "omics" technologies to further our clinical understanding of tendinopathy will increase.
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The proteins ELN and FBN2 are important in extracellular matrix function. The ELN rs2071307 and FBN2 rs331079 gene variants have been associated with soft tissue pathologies. We aimed to determine whether these variants were predisposing... more
The proteins ELN and FBN2 are important in extracellular matrix function. The ELN rs2071307 and FBN2 rs331079 gene variants have been associated with soft tissue pathologies. We aimed to determine whether these variants were predisposing factors for both Achilles tendinopathy (AT) and anterior cruciate ligament (ACL) ruptures. For the AT study, 135 cases (TEN group) and 239 asymptomatic controls were recruited. For the ACL rupture study our cohort consisted of 141 cases (ACL group) and 219 controls. Samples were genotyped for both the ELN rs2071307 and FBN2 rs331079 variants using TaqMan assays. Analysis of variance and chi-squared tests were used to determine whether either variant was associated with AT or ACL rupture with significance set at p<0.05. The GG genotype of the FBN2 variant was significantly over-represented within the TEN group (p=0.035; OR=1.83; 95% CI 1.04-3.25) compared to the CON group. We also found that the frequency of the G allele was significantly differen...
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Recent research has identified DNA sequence variants within genes encoding structural components of the collagen fibril, the basic structural unit of tendons, to modify the risk of carpal tunnel syndrome (CTS). Since the expression of... more
Recent research has identified DNA sequence variants within genes encoding structural components of the collagen fibril, the basic structural unit of tendons, to modify the risk of carpal tunnel syndrome (CTS). Since the expression of these previously associated genes are regulated by cytokine and growth factor signalling pathways, the aim of this study was to determine whether variants within these cell signalling pathway genes, namely interleukin 1β (IL-1β), IL-6, interleukin 6 receptor (IL-6R) and vascular endothelial growth factor A(VEGFA), are also associated with CTS. One hundred and three self-reported Coloured participants, with a history of carpal tunnel release surgery (CTS) and 149 matched control participants (CON) without any reported history of CTS symptoms were genotyped for the functional IL-1β rs16944 (-511C/T), IL-6 rs1800795 (-174G/C), IL-6R rs2228145 (C/A) and VEGFA rs699947 (-2578C/A) variants. Only the IL-6R variant was significantly associated with CTS (p=0.00...
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Angiogenesis-associated signaling is a fundamental component in the remodeling of the extracellular matrix in response to loading. Genes encoding protein components within this signaling cascade are therefore suitable candidates for... more
Angiogenesis-associated signaling is a fundamental component in the remodeling of the extracellular matrix in response to loading. Genes encoding protein components within this signaling cascade are therefore suitable candidates for investigation into ACL injury susceptibility: namely, vascular endothelial growth factor A isoform (VEGFA), kinase insert-domain receptor (KDR), nerve growth factor (NGF), and hypoxia inducible factor-1α (HIF1A). A case-control genetic association study was conducted on 227 asymptomatic control participants and 227 participants with surgically diagnosed ACL ruptures of which 126 participants reported a non-contact mechanism of rupture. All participants were genotyped for seven polymorphisms within the four genes. The VEGFA rs699947 CC genotype (p=0.010, OR: 1.92, 95% CI: 1.17-3.17) was significantly over-represented within participants with non-contact ACL ruptures. The VEGFA rs1570360 GA genotype was significantly over-represented in the CON group (p=0.007, OR: 1.70, 95% CI: 1.16-2.50). Furthermore, the KDR rs2071559 GA genotype was significantly over-represented in the female controls (p=0.023, OR: 2.16, 95% CI: 1.11-4.22). Inferred haplotype analyses also implicated genomic regions spanning the VEGFA and KDR genes. These novel findings suggest that regions within VEGFA and KDR may be implicated in the pathophysiology of ACL ruptures; highlighting the potential biological significance of angiogenesis-associated signaling in the aetiology of ACL ruptures.
Research Interests: Biomedical Engineering, Risk, Orthopaedic, Signal Transduction, Anterior Cruciate Ligament, and 12 moreHumans, Haplotypes, Female, Male, Genetic Association Studies, Rupture, Clinical Sciences, Genotype, Vascular Endothelial Growth Factor, Case Control Studies, Vascular endothelial growth factor receptor, and Gene frequency
Abstract: Extracted from text... Application of human genetics in sports medicine and exercise science International SportMed Journal, Vol. 7 No. 3, 2006, pp. 170-171 http://www. ismj. com Official Journal of FIMS (International... more
Abstract: Extracted from text... Application of human genetics in sports medicine and exercise science International SportMed Journal, Vol. 7 No. 3, 2006, pp. 170-171 http://www. ismj. com Official Journal of FIMS (International Federation of Sports Medicine) 170 ISMJ International SportMed Journal Editorial The application of human genetics in sports medicine and exercise science Dr Malcolm Collins, BSc (Hons), PhD UCT/MRC Research Unit for Exercise Science and Sports Medicine, University of Cape Town, South Africa ...
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Background. Although variants within genes that encode protein components of several biological systems have been associated with athletic performance, limited studies have investigated the collagen genes that encode the structural... more
Background. Although variants within genes that encode protein components of several biological systems have been associated with athletic performance, limited studies have investigated the collagen genes that encode the structural components of connective tissues.Objective. To investigate the association of variants within collagen genes with endurance performance in South African (SA) Ironman triathletes.Methods. A total of 661 white, male participants were recruited from four SA Ironman triathlon events for this genetic case-control association study. All participants were genotyped for COL3A1 rs1800255 (G/A) and COL12A1 rs970547 (A/G).Results. No independent associations were identified between COL3A1 rs1800255 and COL12A1 rs970547 and overall finishing time or time to complete any of the individual components (3.8 km swim, 180 km bike or 42.2 km run) of the 226 km event. The major G+A-inferred pseudo-haplotype, constructed from COL3A1 rs1800255 and COL12A1 rs970547, was, howeve...
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Approximately 64-70% of the variability in joint range of motion (ROM) is heritable. A common variant within a type V collagen (COL5A1) gene is associated with joint range of motion. Like type V collagen, types III, VI and XII collagen... more
Approximately 64-70% of the variability in joint range of motion (ROM) is heritable. A common variant within a type V collagen (COL5A1) gene is associated with joint range of motion. Like type V collagen, types III, VI and XII collagen are also involved in fibril assembly and/or diameter regulation. Mutations within the genes that encode these proteins, COL3A1, COL6A1 and COL12A1, also cause connective tissue hypermobility disorders and phenotypes. The aim of this study was to determine if variants within these genes are associated with measures of joint range of motion. Three hundred and fifty apparently healthy and physically active Caucasian participants were recruited. Anthropometric measurements were taken. Sit-and-reach (SR), straight leg raise (SLR) and total shoulder rotation (ShTR) range of motion were measured. All participants were genotyped for COL3A1 rs1800255, COL6A1 rs35796750 and COL12A1 rs970547. COL3A1 rs1800255, COL6A1 rs35796750 and COL12A1 rs970547 were not significantly associated with sit-and-reach, straight leg raise or total shoulder rotation range of motion. Furthermore, no significant age-genotype interaction effects were identified between the variants and range of motion measurements. None of the variants investigated in this study were significantly associated with any of the measures of range of motion used. Further studies are required to identify additional intrinsic and extrinsic factors that may determine range of motion, including the genetic component.
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Tendons are formed during the second half of embryonic developmentwhen tendon precursor cells deposit narrow-diameter (∼30 nm) collagenfibrils that are parallel to the long axis of the tissue. During post nataldevelopment, the narrow... more
Tendons are formed during the second half of embryonic developmentwhen tendon precursor cells deposit narrow-diameter (∼30 nm) collagenfibrils that are parallel to the long axis of the tissue. During post nataldevelopment, the narrow fibrils are replaced by large-diameter (up to500 nm)fibrils.Theabilityoftendontotransmitforcefrommuscletobone,and to dissipate forces during locomotion, is directly attributable to thecollagen fibrils. How the fibrils are synthesised, how they are alignedparallel to the tendon long axis, and how this arrangement can bereinstated during tendon healing are poorly understood. Ultrastructuralstudies of tendon lesions show the reappearance of narrow-diametercollagen fibrils and cells with slender cytoplasmic protrusions (calledfibripositors) that normally only occur in tendon during embryonicdevelopment. Recapitulation of development is a hypothesis that isgaining increasing support from researchers of tendon disease. A betterunderstanding of the genetic, molecular and environmental cues duringembryonicdevelopmentisexpectedtoprovidebetterinsightsintohowtoimprove the rate and fidelity of tendon repair in mature horses. Tendondevelopment can conveniently be considered to have an early ‘cellular’phaseandasubsequent‘matrix’phase.Inthematrix-dominatedphaseoftendon development 3D scanning electron microscopy of mouse tendonsuggests that fibripositors of the cells are the site of new fibril formationandthemechanicalinterfacebetweenthecellandtheextracellularmatrix.It is hypothesised that fibripositors exert pulling forces on collagen fibrils,and their cellular forces require functional myosin II, which is anintracellular molecular motor that is part of the actinomyosin system. Adetailed understanding of how cells set the tensional homeostasis oftendon is expected to lead to new strategies for regulating collagen fibrilassemblyinhealthandintendinopathy.
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Glucocorticoid hyperactivity in adipose tissue, due to up-regulation of local glucocorticoid reactivation by 11beta-hydroxysteroid dehydrogenase-1 (11HSD1) or of glucocorticoid receptors (GR), may underpin susceptibility to the metabolic... more
Glucocorticoid hyperactivity in adipose tissue, due to up-regulation of local glucocorticoid reactivation by 11beta-hydroxysteroid dehydrogenase-1 (11HSD1) or of glucocorticoid receptors (GR), may underpin susceptibility to the metabolic syndrome. This hypothesis has been tested extensively in subcutaneous adipose tissue (SAT) but inadequately in visceral adipose tissue (VAT). The aim of the study was therefore to examine expression of 11HSD1, GRalpha and hexose-6-phosphate dehydrogenase (H6PDH), which supplies cofactor for 11HSD1, in abdominal adipose tissue compartments and to characterize their relation to metabolic syndrome parameters. A cross-sectional study including 26 premenopausal South African women. Biopsies were taken for measurement of mRNA levels by real-time polymerase chain reaction (RT-PCR) and 11HSD1 activity from VAT, and deep and superficial SAT compartments during elective surgery. Prior to surgery, blood pressure, blood lipid profile, body composition [by dual X-ray absorptiometry (DEXA) scan], body fat distribution [by computed tomography (CT) scan], and glucose tolerance were determined. 11HSD1 activity (P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) was higher in VAT than SAT, but 11HSD1 and GRalpha mRNA levels were not statistically different between compartments. 11HSD1 mRNA levels in superficial SAT correlated with VAT volume (R = 0.57, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), insulin sensitivity calculated from the oral glucose tolerance test (OGTT) (R = -0.52, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.016) and blood pressure (R = 0.48, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.016). Apart from a correlation between deep SAT 11HSD1 activity and blood pressure (R = 0.72, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), glucocorticoid action in deep SAT and VAT depots was not significantly associated with any metabolic syndrome parameters. Increased capacity for glucocorticoid regeneration in superficial SAT but not VAT is associated with visceral adiposity and other features of the metabolic syndrome in women.
Research Interests: Metabolic syndrome, South Africa, Humans, Female, Clinical, and 15 moreBody Composition, Regression Analysis, Clinical Sciences, South African, Middle Aged, Adult, Glucose Tolerance Test, Clinical Endocrinology, Cross Sectional Studies, Glucocorticoids, Premenopause, Metabolic Syndrome X, reverse transcriptase polymerase chain reaction, hydrocortisone, and Paediatrics and reproductive medicine
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Abstract: Extracted from text... Application of human genetics in sports medicine and exercise science International SportMed Journal, Vol. 7 No. 3, 2006, pp. 170-171 http://www. ismj. com Official Journal of FIMS (International... more
Abstract: Extracted from text... Application of human genetics in sports medicine and exercise science International SportMed Journal, Vol. 7 No. 3, 2006, pp. 170-171 http://www. ismj. com Official Journal of FIMS (International Federation of Sports Medicine) 170 ISMJ International SportMed Journal Editorial The application of human genetics in sports medicine and exercise science Dr Malcolm Collins, BSc (Hons), PhD UCT/MRC Research Unit for Exercise Science and Sports Medicine, University of Cape Town, South Africa ...
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Research Interests: Nutrition and Dietetics, Obesity, British, Adolescent, Near Infrared, and 15 moreMedicine, Animal Production, Adipose tissue, South Africa, Humans, Female, Middle Aged, Adult, Spectrum analysis, European Continental Ancestry Group, Food Sciences, Body Fat, Reference Values, Infrared Rays, and Adiposity
Achilles tendinopathy (AT) is associated with pain and altered ultrasound (US) and color Doppler (CD) findings. However, the relationship between them is equivocal, perhaps because previous studies have only used the VISA‐A scale as the... more
Achilles tendinopathy (AT) is associated with pain and altered ultrasound (US) and color Doppler (CD) findings. However, the relationship between them is equivocal, perhaps because previous studies have only used the VISA‐A scale as the measure of tendon pain. To determine the relationship between tendon US and CD findings and self‐reported pain using the VISA‐A, Short‐form McGill Pain Questionnaire (sf‐MPQ), and Short‐form Brief Pain Inventory (sf‐BPI). Recreational athletes with AT rated their tendon pain on the VISA‐A, sf‐MPQ, and sf‐BPI. The Achilles tendons of runners with (TEN, n = 127) and without tendinopathy (CON, n = 103) were examined using conventional grayscale ultrasound and CD settings. Participants with AT had thicker tendons (mm) (median [IQR]) [TEN‐ 6.2 (5.3‐7.9) vs CON 5.5 (4.8; 6.0)] (P < 0,001); abnormal tendon ultrasound appearances (P = .001); and more neovessels than healthy controls (P < .001). No differences were noted between tendon pain scores and US or CD abnormalities (P > .05). Tendinopathy is associated with US and CD changes that may be of some prognostic value. The mismatch between patient‐reported symptoms and US and CD findings could be indicative of the need to standardize US and CD protocols in order to enhance comparisons across the studies.
Variants within genes that encode proteins regulating fibrillogenesis such as BGN (rs1126499 C&amp;amp;amp;amp;amp;amp;amp;amp;gt;T, rs1042103 C&amp;amp;amp;amp;amp;amp;amp;amp;gt;T), COL5A1 (rs12722... more
Variants within genes that encode proteins regulating fibrillogenesis such as BGN (rs1126499 C&amp;amp;amp;amp;amp;amp;amp;amp;gt;T, rs1042103 C&amp;amp;amp;amp;amp;amp;amp;amp;gt;T), COL5A1 (rs12722 C&amp;amp;amp;amp;amp;amp;amp;amp;gt;T) and DCN (rs516115 C&amp;amp;amp;amp;amp;amp;amp;amp;gt;T) have been associated with susceptibility to anterior cruciate ligament (ACL) ruptures. A miRNA mediated transcript instability was proposed for the COL5A1 association. The study aims were: (i) to investigate the association of inferred allele combinations across the COL5A1 3&amp;amp;amp;amp;amp;amp;amp;amp;#39;-UTR, BGN and DCN genes with susceptibility to ACL rupture; and (ii) to use an in silico approach to identify miRNA binding sites common to these risk associated allele combinations. Case-control association study METHODS: Allele combinations were generated from the genotype data of the BGN (rs1126499, rs1042103), COL5A1 (rs12722) and DCN (rs516115) loci for 227 participants with surgically diagnosed ACL ruptures and 234 asymptomatic controls. Statistical analyses between the CON and ACL groups as well as sex-specific interactions were investigated. Significance was accepted at p&amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05. miRNA binding sites within these genes were identified using DIANA tools. Several sex-specific inferred allele combinations were associated with altered susceptibility and miRNA (miR-22, miR-27b, miR-140, miR-199a, miR-199b, miR-299, miR-338 and miR-484) recognition motifs were identified in range of these susceptibility loci. In conclusion, this study has implicated inferred allele combinations across BGN (rs1126499, rs1042103), COL5A1 (rs12722) and DCN (rs516115) as well as eight miRNA recognition sequences in susceptibility to ACL rupture. The biological significance of these genomic signatures needs to be explored to understand their effect on the ligaments functional capacity.
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Genes encoding for tenascin C and a subunit of type V collagen have previously been reported to be associated with Achilles tendon injuries. Types XII and XIV collagen may be involved in similar biological processes as these proteins in... more
Genes encoding for tenascin C and a subunit of type V collagen have previously been reported to be associated with Achilles tendon injuries. Types XII and XIV collagen may be involved in similar biological processes as these proteins in tendons. The aim of this study was therefore to test the association between polymorphisms within COL12A1 and COL14A1 and Achilles tendon injuries. Restriction fragment length polymorphism (RFLP) analysis was used to identify the relative frequencies of two polymorphisms within each of the COL12A1 and COL14A1 genes within 137 subjects with clinical symptoms of Achilles tendon injuries, consisting of 93 with Achilles tendinopathy and 44 with Achilles tendon rupture, and 131 asymptomatic control subjects. No statistically significant differences were identified in the genotype, allele or haplotype distributions between the affected and control subjects. The findings from this study suggest that although COL12A1 and COL14A1 are involved in similar biolo...
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Background Achilles tendinopathy and tendon rupture are multifactorial conditions for which specific genetic risk factors have been identified. The matrix metalloproteinase 3 gene (MMP3) previously been associated with risk of developing... more
Background Achilles tendinopathy and tendon rupture are multifactorial conditions for which specific genetic risk factors have been identified. The matrix metalloproteinase 3 gene (MMP3) previously been associated with risk of developing Achilles tendinopathy. The MMP-3 enzyme catalytically degrades several substrates and is a key regulator of extracellular matrix (ECM) homeostasis. The ADAMTS5, ADAM12 and TIMP2 genes encode enzymes that are also important regulators of ECM homeostasis and integrity. Non-synonymous variants within the metalloproteinases ADAMTS5 (rs226794) and ADAM12 (rs3740199) genes have been associated with osteoarthritis, also a complex multifactorial condition of the ECM. TIMP2, a metalloprotease inhibitor, maintains homeostasis in the ECM by inhibiting ADAM, ADAMTS and MMP functions. Objective To determine if selected non-synonymous polymorphism within the ADAMTS5 rs226794, ADAM12 rs3740199 and TIMP2 rs4789932 genes are associated with risks of Achilles tendon pathology (ATP) in two independent populations. Methods 210 (114 cases with ATP and 96 asymptomatic controls) South African Caucasian participants and 200 (58 cases with ATP and 142 asymptomatic controls) Australian Caucasian participants were recruited for this case-control genetic association study. All participants were genotyped using TaqMan technology for the ADAMTS5 G/A rs226794, ADAM12 G/C rs3740199, and TIMP2 C/T rs4789932 polymorphisms. Results The genotype frequency of the TIMP2 rs4789932 variant was significantly different (P=0.016) between the ATP (CC, 26.6%; CT, 56.6%; TT, 16.8%) and CON (CC, 36.4%; CT, 42.4%; TT, 21.2%) groups. There were no significant associations between the ADAMTS5 rs226794 (P=0.323) and ADAM12 rs3740199 (P=0.633) variants and risk of ATP. Conclusion This study shows for the first time that a TIMP2 polymorphism is associated with ATP in a combined South African and Australian Caucasian cohort.
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Abstract The COL5A1 and COL12A1 variants are independently associated with modulating the risk of anterior cruciate ligament (ACL) rupture in females. The objective of this study was to further investigate if COL3A1 and COL6A1 variants... more
Abstract The COL5A1 and COL12A1 variants are independently associated with modulating the risk of anterior cruciate ligament (ACL) rupture in females. The objective of this study was to further investigate if COL3A1 and COL6A1 variants independently, as well as, collagen gene-gene interactions, modulate ACL rupture risk. Three hundred and thirty-three South African (SA, n = 242) and Polish (PL, n = 91) participants with diagnosed ACL ruptures and 378 controls (235 SA and 143 PL) were recruited. Participants were genotyped for COL3A1 rs1800255 G/A, COL5A1 rs12722 (T/C), COL6A1 rs35796750 (T/C) and COL12A1 rs970547 (A/G). No significant associations were identified between COL6A1 rs35796750 and COL3A1 rs1800255 genotypes and risk of ACL rupture in the SA cohort. The COL3A1 AA genotype was, however, significantly (p = 0.036) over-represented in the PL ACL group (9.9%, n = 9) when compared to the PL control (CON) group (2.8%, n = 4). Although there were genotype distribution differences between the SA and PL cohorts, the T+A-inferred pseudo-haplotype constructed from COL5A1 and COL12A1 was significantly over-represented in the female ACL group when compared to the female CON group within the SA (T+A ACL 50.5%, T+A CON 38.1%, p = 0.022), PL (T+A ACL 56.3%, T+A CON 36.3%, p = 0.029) and combined (T+A ACL 51.8%, T+A CON 37.5%, p = 0.004) cohorts. In conclusion, the novel main finding of this study was a significant interaction between the COL5A1 rs12722 T/C and COL12A1 rs970547 A/G variants and risk of ACL injury. These results highlight the importance of investigating gene-gene interactions in the aetiology of ACL ruptures in multiple independent cohorts.
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The incidence of acute and chronic conditions of the tendo Achillis appear to be increasing. Causation is multifactorial but the role of inherited genetic elements and the influence of environmental factors altering gene expression are... more
The incidence of acute and chronic conditions of the tendo Achillis appear to be increasing. Causation is multifactorial but the role of inherited genetic elements and the influence of environmental factors altering gene expression are increasingly being recognised. Certain individuals’ tendons carry specific variations of genetic sequence that may make them more susceptible to injury. Alterations in the structure or relative amounts of the components of tendon and fine control of activity within the extracellular matrix affect the response of the tendon to loading with failure in certain cases. This review summarises present knowledge of the influence of genetic patterns on the pathology of the tendo Achillis, with a focus on the possible biological mechanisms by which genetic factors are involved in the aetiology of tendon pathology. Finally, we assess potential future developments with both the opportunities and risks that they may carry. Cite this article: Bone Joint J 2013;95-B...
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Research Interests: Australia, Biology, Molecular Genetics, Medicine, Musculoskeletal Injury Prevention, and 15 moreSouth Africa, Humans, Female, Male, Genetic Association Studies, Tendinopathy, Risk factors, Adult, Sports Sciences, Curriculum and Pedagogy, Soft Tissue Injuries, Body Weight, Risk Factors, Case Control Studies, and Gene frequency
This study compared differences in maximal strength and aerobic capacity and symptoms of fatigue and depression in athletes with acquired training intolerance (ATI) and control athletes (CON) matched for age and current training volume... more
This study compared differences in maximal strength and aerobic capacity and symptoms of fatigue and depression in athletes with acquired training intolerance (ATI) and control athletes (CON) matched for age and current training volume who did not have symptoms of excessive or chronic fatigue associated with their sporting activity. University of Cape Town, Sports Science Institute of South Africa. Twenty ATI and 10 CON athletes participated in the trial. Although the ATI athletes reported symptoms of excessive fatigue during exercise, or symptoms of fatigue that occurred at rest and during activities of daily living, they did not fulfill the criteria for a diagnosis of chronic fatigue syndrome. A training and comprehensive medical history was recorded from all subjects. The Beck Depression Inventory Short Form (BDI-SF) was used to assess levels of depression in both ATI and control subjects. Maximal force output during a 5-second isometric voluntary knee extensor muscle contraction, and maximal aerobic capacity (VO2max), maximal heart rate (HRmax), and maximal blood lactate concentrations during a treadmill running test were measured in all subjects. There were no differences in maximal isometric force output, peak treadmill running speed, VO2max, HRmax, or blood lactate concentration at rest or after maximal exercise testing between the ATI and CON athletes. However, the BDI-SF scores were higher in the ATI (7.7 +/- 6.6 arbitrary units) than in the CON athletes (1.7 +/- 1.5 arbitrary units; (P = 0.0052). These findings suggest that the symptoms of excessive fatigue and acquired training intolerance described by these ATI athletes do not affect their maximal isometric and maximal aerobic capacity, and may be associated with psychologic depression in these athletes.
Research Interests: Depression, Fatigue, Medicine, Sports, Humans, and 6 moreChronic Disease, Female, Male, Adult, Oxygen Consumption, and Exercise Tolerance
Objectives Achilles tendon pathology (ATP) is a multifactorial condition for which genetic risk factors have been identified. The ADAMTS, ADAM12 and TIMP2 genes encode enzymes that are important regulators of tendon homeostasis. ADAMTS2... more
Objectives Achilles tendon pathology (ATP) is a multifactorial condition for which genetic risk factors have been identified. The ADAMTS, ADAM12 and TIMP2 genes encode enzymes that are important regulators of tendon homeostasis. ADAMTS2 and ADAMTS14 proteins are procollagen N-propeptidases for pro-collagen type I, type II, and type III. ADAMTS2, like COL5A1, has been linked to Ehlers–Danlos syndrome. Variants within ADAMTS5 and ADAM12 have been associated with osteoarthritis. TIMP2, a metalloprotease inhibitor, ...
A COL5A1 gene variant was shown to be associated with chronic Achilles tendinopathy in a South African population. The aim of this case-control genetic association study was to investigate the BstUI and DpnII restriction fragment length... more
A COL5A1 gene variant was shown to be associated with chronic Achilles tendinopathy in a South African population. The aim of this case-control genetic association study was to investigate the BstUI and DpnII restriction fragment length polymorphisms (RFLP) in a second population from Australia and to identify a predisposing haplotype for Achilles tendinopathy in both populations. 85 Australian and 93 South African patients with tendinopathy, as well as 210 Australian and 132 white South African control subjects were genotyped for the BstUI (rs12722) and DpnII (rs13946) RFLP, as well as markers rs10858286, rs3196378, rs11103544, rs4504708 and rs3128575. The BstUI RFLP (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and marker rs3196378 (p = 0.016) were associated with chronic Achilles tendinopathy in Australian subjects. Individuals within both populations with a CC genotype for the BstUI RFLP had a significantly decreased risk of developing tendinopathy versus any other genotypes (Australian odds ratio 0.42, 95% CI 0.20 to 0.86, p = 0.017). The TC inferred haplotype (rs12722, rs3196378) was found to be overrepresented (global p = 0.008) in the South African tendinopathy group compared with all other haplotypes. The BstUI RFLP is associated with chronic Achilles tendinopathy in a second population and a region within the COL5A1 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; untranslated region may predispose individuals to an increased risk of developing chronic Achilles tendinopathy.
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The TNC gene has previously been associated with Achilles tendinopathy (AT) in a South African population. The aims of this study were (i) to investigate the association of single nucleotide polymorphisms within the TNC gene, and the... more
The TNC gene has previously been associated with Achilles tendinopathy (AT) in a South African population. The aims of this study were (i) to investigate the association of single nucleotide polymorphisms within the TNC gene, and the additional candidate gene, COL27A1, with AT in two populations, and (ii) to identify if there is a risk haplotype for AT in both populations. Three hundred and thirty nine healthy control participants (CON) and 179 participants clinically diagnosed with AT (TEN) from South Africa and Australia, were genotyped for variants: rs4143245, rs1249744, rs753085, rs946053 (COL27A1) and rs13321, rs2104772, rs1330363 (TNC). Haplotypes were inferred using the genotype data. The rs2104772 (p = 0.017) and rs1330363 (p = 0.020) variants within TNC showed a significant allele association with AT. The GCA haplotype (rs946053-rs13321-rs2104772) occurred significantly more frequently in TEN participants compared to CON (27% vs. 18%; p = 0.019). This study further implicat...
Research Interests: Biomedical Engineering, Australia, Molecular Genetics, Orthopaedic, Musculoskeletal Injury Prevention, and 13 moreMolecular Biology and genetics, South Africa, Humans, Female, Male, Tendinopathy, Clinical Sciences, Genotype, Tenascin-C, Achilles tendon, European Continental Ancestry Group, Tenascin, and Gene frequency
Measuring the DNA telomere length of skeletal muscle in experienced endurance runners may contribute to our understanding of the effects of chronic exposure to endurance exercise on skeletal muscle. This study compared the minimum... more
Measuring the DNA telomere length of skeletal muscle in experienced endurance runners may contribute to our understanding of the effects of chronic exposure to endurance exercise on skeletal muscle. This study compared the minimum terminal restriction fragment (TRF) length in the vastus lateralis muscle of 18 experienced endurance runners (mean age: 42 +/- 7 years) to those of 19 sedentary individuals (mean age: 39 +/- 10 years). The runners had covered almost 50,000 km in training and racing over 15 years. Minimum TRF lengths measured in the muscle of both groups were similar (P = 0.805) and within the normal range. Minimum TRF length in the runners, however, was inversely related to their years spent running (r = -0.63, P = 0.007) and hours spent training (r = -0.52, P = 0.035). Therefore, since exposure to endurance running may influence minimum TRF length, and by implication, the proliferative potential of the satellite cells, chronic endurance running may be seen as a stressor to skeletal muscle.
Research Interests:
Abstract Elite sporting performance results from the combination of innumerable factors, which interact with one another in a poorly understood but complex manner to mould a talented athlete into a champion. Within the field of sports... more
Abstract Elite sporting performance results from the combination of innumerable factors, which interact with one another in a poorly understood but complex manner to mould a talented athlete into a champion. Within the field of sports science, elite performance is understood to be the result of both training and genetic factors.
Abstract Of 371 athletes (62% of all finishers) whose weights were measured before and after the 226 km South African Ironman Triathlon, the athlete who gained the most weight (3.6 kg) during the race was the only competitor to develop... more
Abstract Of 371 athletes (62% of all finishers) whose weights were measured before and after the 226 km South African Ironman Triathlon, the athlete who gained the most weight (3.6 kg) during the race was the only competitor to develop symptomatic hyponatraemia. During recovery, he excreted an excess of 4.6 litres of urine. This case report again confirms that symptomatic hyponatraemia is caused by considerable fluid overload independent of appreciable NaCl losses.
Background: Subjects exercising without fluid ingestion in desert heat terminated exercise when the total loss in body weight exceeded 7%. It is not known if athletes competing in cooler conditions with free access to fluid terminate... more
Background: Subjects exercising without fluid ingestion in desert heat terminated exercise when the total loss in body weight exceeded 7%. It is not known if athletes competing in cooler conditions with free access to fluid terminate exercise at similar levels of weight loss. Objectives: To determine any associations between percentage weight losses during a 224 km Ironman triathlon, serum sodium concentrations and rectal temperatures after the race, and prevalence of medical diagnoses.
Full Text: It has been well recognized that multiple factors, whether individually or in combination, contribute to noncontact anterior cruciate ligament (ACL) injury. The ongoing mission of the ACL Research Retreat is to bring clinicians... more
Full Text: It has been well recognized that multiple factors, whether individually or in combination, contribute to noncontact anterior cruciate ligament (ACL) injury. The ongoing mission of the ACL Research Retreat is to bring clinicians and researchers together to present and discuss the most recent advances in ACL injury epidemiology, risk factor identification, and injury-risk screening and prevention strategies and to identify future research directives.