Search

Background: The 56km Two Oceans ultra-marathon (TOM), in Cape Town, South Africa, was cancelled in 2020 and 2021 because of the COVID-19 pandemic. Since most other road running events were also cancelled during this period, we hypothesized that most athletes who entered TOM 2022 would be inadequately trained, which would negatively affect performance. However, many world records were broken post-lockdown, and therefore the performance, specifically of the elite athletes, during TOM might actually improve. The aim of this analysis was to evaluate the impact of the COVID-19 pandemic on performance in TOM 2022 compared to the 2018 event., Methods: Performance data during the two events, as well as the 2021 Cape Town marathon, was extracted from public databases., Results: Fewer athletes entered TOM 2022 (N.=4741) compared to TOM 2018 (N.=11,702), of which more were male (2022: 74.5% vs. 2018: 70.4%, P<0.05) and in the 40+ age-group categories. Compared to 2018 (11.3%), fewer athletes did not finish TOM 2022 (3.1%). Only 10.2% of the finishers completed the 2022 race during the last 15-minutes prior to the cut-off, compared to 18.3% in 2018. There were no differences in the average 2022 finishing time of the subset of 290 athletes whose times were compared to their 2018 performance. There was no difference in the TOM 2022 performance of athletes who had completed the 2021 Cape Town marathon, 6-months earlier, when compared to those who had not entered the marathon., Conclusions: Although there were fewer entrants, most athletes who entered knew that they were adequately trained to complete TOM 2022, with the top runners breaking course records. There was therefore no impact of the pandemic on performance during TOM 2022.

Previous small-scale studies have shown an association between the COL5A1 gene and anterior cruciate ligament (ACL) injury risk. In this larger study, the genotype and allele frequency distributions of the COL5A1 rs12722 C/T and rs10628678 AGGG/deletion (AGGG/-) indel variants were compared between participants: (i) with ACL injury in independent and combined cohorts from South-Africa (SA) and Australia (AUS) vs controls (CON), and (ii) with any ligament (ALL) or only ACL injury in a Japanese (JPN) cohort vs CON. Samples were collected from SA (235 cases; 232 controls), AUS (362 cases; 80 controls) and JPN (500 cases; 1,403 controls). Genomic DNA was extracted and genotyped. Distributions were compared, and inferred haplotype analyses performed. No independent associations were noted for rs12722 or rs10628678 when the combined SA + AUS cohort was analysed. However, the C-deletion (rs12722-rs10628678) inferred haplotype was under-represented ( p  = 0.040, OR = 0.15, CI = 0.04-0.56), while the T-deletion inferred haplotype was over-represented in the female SA + AUS ACL participants versus controls ( p  < 0.001, OR = 4.74, CI = 1.66-13.55). Additionally, the rs12722 C/C genotype was under-represented in JPN CON vs ACL ( p  = 0.039, OR = 0.52, 0.27-1.00), while the rs10628678 -/- genotype was associated with increased risk of any ligament injuries ( p  = 0.035, OR = 1.31, CI = 1.02-1.68) in the JPN cohort. Collectively, these results highlight that a region within the COL5A1 3'-UTR is associated with ligament injury risk. This must be evaluated in larger cohorts and its functional relevance to the structure and capacity of ligaments and joint biomechanics be explored. Highlights The COL5A1 T-deletion inferred haplotype (rs12722-rs10628678) was associated with an increased risk of ACL rupture in the combined SA and AUS female participants.The COL5A1 C-deletion inferred haplotype (rs12722-rs10628678) was associated with a decreased risk of ACL rupture in the combined SA and AUS female participants.The COL5A1 rs12722 C/C and rs10628678 -/- genotypes were associated with increased risk of ACL rupture and of ligament injuries in JPN, respectively.A region within the COL5A1 3'-UTR is associated with risk of ligament injury, including ACL rupture, and therefore the functional significance of this region on ligament capacity and joint biomechanics requires further exploration.

Objectives: The main assessment tool for Achilles tendinopathy (AT) is the VISA-A. However, the VISA-A only assesses the physical impairments that result from tendon pain. This study sought to describe and assess tendon pain using other multidimensional pain scales; the short forms of the McGill pain questionnaire (sf-MPQ) and the Brief Pain Inventory (sf-BPI)., Design: Cross sectional observational study., Methods: 124 recreational runners with clinically confirmed mid-portion Achilles tendinopathy for at least 3 months were recruited from Cape Town, South Africa. They described and rated their tendinopathy symptoms by completing the VISA-A, sf-BPI and sf-MPQ questionnaires., Results: Tendon pain was largely described as a sensory type of pain with minimal affective elements. Sixty percent described their pain as aching. Significant proportions described it as tender (52.9%), throbbing (33.9%), hot burning (24.8%) and 33.8% ranked it as discomfiting or worse on the pain intensity score of the sf-MPQ. Tendon pain interfered with mood in 50.8% of the participants as well as with walking ability (72.5%), sleep (34.8%) and enjoyment of life (54.2%)., Conclusions: Tendon pain was described using a variety of adjectives which may suggest that AT has clinical subtypes. Tendon pain interferes with more than just physical function. Therefore, the recommendation is to conduct further studies using various pain questionnaires to elicit more details and better understand the nature of Achilles tendon pain., (Copyright © 2019 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Rotator cuff tendinopathy (RCT), anterior cruciate ligament (ACL) ruptures, and carpal tunnel syndrome (CTS), are examples of chronic (RCT and CTS) and acute (ACL ruptures) musculoskeletal soft tissue injuries. These injuries are multifactorial in nature, with several identified intrinsic and extrinsic risk factors. Previous studies have implicated specific sequence variants within genes encoding structural and regulatory components of the extracellular matrix of tendons and/ligaments to predispose individuals to these injuries. An example, includes the association of sequence variants within the apoptotic regulatory gene, caspase-8 (CASP8) with other musculoskeletal injury phenotypes, such as Achilles tendinopathy. The primary aim of this study was, therefore, to investigate previously implicated DNA sequence variants within CASP8: rs3834129 (ins/del) and rs1045485 (G/C), and the rs13113 (T/A) identified using a whole exome sequencing approach, with risk of musculoskeletal injury phenotypes (RCT, ACL ruptures, and CTS) in three independent studies. In addition, the aim was to implicate a CASP8 genomic interval in the modulation of risk of RCT, ACL ruptures, or CTS. It was found that the AA genotype of CASP8 rs13113 (T/A) was independently associated with increased risk for CTS. In addition, it was found that the del-C haplotype (rs3834129-rs1045485) was significantly associated with non-contact ACL ruptures, which is in alignment with previous research findings. Collectively, the results of this study implicate the apoptosis pathway as biologically significant in the underlying pathogenesis of musculoskeletal injury phenotypes. These findings should be repeated in larger sample cohorts and across different populations. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:680-688, 2020., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objectives: To investigate the functional effect of genetic polymorphisms of the inflammatory pathway on structural extracellular matrix components (ECM) and the susceptibility to an anterior cruciate ligament (ACL) injury., Design: Laboratory study, case-control study., Methods: Eight healthy participants were genotyped for interleukin (IL)1B rs16944 C>T and IL6 rs1800795 G>C and classified into genetic risk profile groups. Differences in type I collagen (COL1A1), type V collagen (COL5A1), biglycan (BGN) and decorin (DCN) gene expression were measured in fibroblasts either unstimulated or following IL-1β, IL-6 or tumor necrosis factor (TNF)-α treatment. Moreover, a genetic association study was conducted in: (i) a Swedish cohort comprised of 116 asymptomatic controls (CON) and 79 ACL ruptures and (ii) a South African cohort of 100 CONs and 98 ACLs. Participants were genotyped for COL5A1 rs12722 C>T, IL1B rs16944 C>T, IL6 rs1800795 G>C and IL6R rs2228145 G>C., Results: IL1B high-risk fibroblasts had decreased BGN (p=0.020) and COL5A1 (p=0.012) levels after IL-1β stimulation and expressed less COL5A1 (p=0.042) following TNF-α treatment. Similarly, unstimulated IL6 high-risk fibroblasts had lower COL5A1 (p=0.012) levels than IL6 low-risk fibroblasts. In the genetic association study, the COL5A1-IL1B-IL6 T-C-G (p=0.034, Haplo-score 2.1) and the COL5A1-IL1B-IL6R T-C-A (p=0.044, Haplo-score: 2.0) combinations were associated with an increased susceptibility to ACL injury in the Swedish cohort when only male participants were evaluated., Conclusions: This study shows that polymorphisms within genes of the inflammatory pathway modulate the expression of structural and fibril-associated ECM components in a genetic risk depended manner, contributing to an increased susceptibility to ACL injuries., (Copyright © 2019 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Musculoskeletal soft tissue injuries are complex phenotypes with genetics being one of many proposed risk factors. Case-control association studies using the candidate gene approach have predominately been used to identify risk loci for these injuries. However, the ability to identify all risk conferring variants using this approach alone is unlikely. Therefore, this study aimed to further define the genetic profile of these injuries using an integrated omics approach involving whole exome sequencing and a customised analyses pipeline. The exomes of ten exemplar asymptomatic controls and ten exemplar cases with Achilles tendinopathy were individually sequenced using a platform that included the coverage of the untranslated regions and miRBase miRNA genes. Approximately 200 000 variants were identified in the sequenced samples. Previous research was used to guide a targeted analysis of the genes encoding the tenascin-C (TNC) glycoprotein and the α1 chain of type XXVII collagen (COL27A1) located on chromosome 9. Selection of variants within these genes were; however, not predetermined but based on a tiered filtering strategy. Four variants in TNC (rs1061494, rs1138545, rs2104772 and rs1061495) and three variants in the upstream COL27A1 gene (rs2567706, rs2241671 and rs2567705) were genotyped in larger Achilles tendinopathy and anterior cruciate ligament (ACL) rupture sample groups. The CC genotype of TNC rs1061494 (C/T) was associated with the risk of Achilles tendinopathy (p = 0.018, OR: 2.5 95% CI: 1.2-5.1). Furthermore, the AA genotype of the TNC rs2104772 (A/T) variant was significantly associated with ACL ruptures in the female subgroup (p = 0.035, OR: 2.3 95% CI: 1.1-5.5). An inferred haplotype in the TNC gene was also associated with the risk of Achilles tendinopathy. These results provide a proof of concept for the use of a customised pipeline for the exploration of a larger genomic dataset. This approach, using previous research to guide a targeted analysis of the data has generated new genetic signatures in the biology of musculoskeletal soft tissue injuries., Competing Interests: The authors have declared that no competing interests exist.

In many developing countries, including South Africa, water scarcity has resulted in poor sanitation practices. The majority of the sanitation infrastructures in those regions fail to meet basic hygienic standards. This along with the lack of proper sewage/wastewater infrastructure creates significant environmental and public health concerns. A self-sustained, waterless "Nano Membrane Toilet" (NMT) design was proposed as a result of the "Reinvent the Toilet Challenge" funded by the Bill and Melinda Gates Foundation. A "cradle-to-grave" life cycle assessment (LCA) approach was adopted to study the use of NMT in comparison with conventional pour flush toilet (PFT) and urine-diverting dry toilet (UDDT). All three scenarios were applied in the context of South Africa. In addition, a Quantitative Microbial Risk Assessment (QMRA) was used to reflect the impact of the pathogen risk on human health. LCA study showed that UDDT had the best environmental performance, followed by NMT and PFT systems for all impact categories investigated including human health, resource and ecosystem. This was mainly due to the environmental credits associated with the use of urine and compost as fertilizers. However, with the incorporation of the pathogen impact into the human health impact category, the NMT had a significant better performance than the PFT and UDDT systems, which exhibited an impact category value 4E + 04 and 4E + 03 times higher, respectively. Sensitivity analysis identified that the use of ash as fertilizer, electricity generation and the reduction of NOx emissions were the key areas that influenced significantly the environmental performance of the NMT system., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

The angiogenesis-signalling pathway is a physiological response after mechanical loading to promote matrix remodelling and thereby maintain tissue homeostasis. Studies have shown increased expression of angiogenic molecules in response to loading and in ruptured ligaments. Recently, polymorphisms within the vascular endothelial growth factor A (VEGFA) and kinase insert-domain receptor (KDR) genes were associated with risk of anterior cruciate ligament (ACL) ruptures and Achilles tendinopathy in Caucasian study groups. A case-control genetic association study was conducted on 100 controls and 98 participants with surgically-diagnosed ACL ruptures; of which 51 participants reported non-contact mechanism of injury (NON). All participants were genotyped for five functional polymorphisms: VEGFA (rs699947, rs1570360, rs2010963) and KDR (rs2071559, rs1870377). Haplotypes were inferred. In the male participants, the KDR rs2071559 AG genotype was significantly over-represented (P = 0.048, OR: 1.90, 95% CI: 1.00-3.59) in the controls. Furthermore, the GG genotype was significantly under-represented in the male controls compared to the male ACL group (P = 0.018, OR: 2.77, 95% CI: 1.17-6.55) and the male NON subgroup (P = 0.013, OR: 3.26, 95% CI: 1.24-8.58). Haplotype analysis implicated the KDR gene in all participants and in male participants separately. Collectively, these results implicate the angiogenesis-signalling pathway as a potentially key biological pathway contributing to ACL injury susceptibility.

Sport and Exercise Medicine is one of the important subspecialties of 21st century healthcare contributing to improving the physical function, health, and vitality of populations while reducing the prevalence of lifestyle-related diseases. Moreover, sport and exercise are associated with injuries such as Achilles tendinopathy, which is a common tendon injury. The angiogenesis-associated signaling pathway plays a key role in extracellular matrix remodeling, with increased levels of angiogenic cytokines reported after cyclic stretching of tendon fibroblasts. We investigated the variants in angiogenesis genes in relation to the risk of Achilles tendinopathy in two population samples drawn independently from South Africa (SA) and the United Kingdom (UK). The study sample comprised 120 SA and 130 UK healthy controls, and 108 SA and 87 UK participants with Achilles tendinopathy. All participants were genotyped for five functional polymorphisms in the vascular endothelial growth factor, A isoform (VEGFA) (rs699947, rs1570360, rs2010963) and kinase insert-domain receptor (KDR) genes (rs1870377, rs2071559). The VEGFA A-G-G inferred haplotype was associated with an increased risk of Achilles tendinopathy in the SA group (15% in controls vs. 20% in cases, p = 0.048) and the combined SA+UK group (14% in controls vs. 20% in cases, p = 0.009). These new findings implicate the VEGFA gene with Achilles tendinopathy risk, while highlighting the potential biological significance of the angiogenesis signaling pathway in the etiology of Achilles tendinopathy. The evidence suggesting a genetic contribution to the susceptibility of sustaining a tendon injury is growing. We anticipate that high-throughput and multi-omics approaches, building on genomics, proteomics, and metabolomics, may soon uncover the pathophysiology of many diseases in the field of Sports and Exercise Medicine, as a new frontier of global precision medicine.

Objective: Dyslipidaemia can lead to the development of atherosclerosis and cardiovascular disease (CVD), however its prevalence has been shown to differ between ethnic groups in South Africa (SA). Therefore the aim of this study was to investigate ethnic differences in the association between serum lipid levels and polymorphisms within genes involved in lipid metabolism in black and white SA women., Methods: In a convenient sample of 234 white and 209 black SA women of Xhosa ancestry, body composition (DXA) and fasting serum lipids were measured. Participants were genotyped for the cholesteryl ester transfer protein (CETP, rs708272, B1/B2), lipoprotein lipase (LPL, rs328, S/X), hepatic lipase (LIPC, rs1800588, C/T) and proprotein convertase subtilisin/kexin type 9 (PCSK9, rs28362286, C/X) polymorphisms., Results: Compared to white women, black women had lower concentrations of serum total cholesterol (TC, P < 0.001), low density lipoprotein cholesterol (LDL-C, P < 0.001), high density lipoprotein cholesterol (HDL-C, P < 0.001) and triglycerides (TG, P < 0.001). There were significant differences in the genotype and allele frequency distributions between black and white women for the LPL S/X (P < 0.001), PCSK9 C679X (P = 0.002) and LIPC 514C/T (P < 0.001) polymorphisms. In black women only, there were genotype effects on serum lipid levels. Specifically, women with the LPL SX genotype had lower TC and LDL-C and higher HDL-C concentrations than those with the SS genotype and women with the CETP B2 allele had lower LDL-C concentrations than those with the B1B1 genotype., Conclusion: Polymorphisms within the LPL and CETP genes were associated with a more protective lipid profile in black, but not white SA women. This supports the hypothesis that the more favorable lipid profile of black compared to white SA women is associated with polymorphisms in lipid metabolism genes, specifically the LPL and CETP genes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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.

This study investigated interactions between dietary fat intake and IL-6 polymorphisms on obesity and serum lipids in black and white South African (SA) women. Normal-weight and obese, black and white women underwent measurements of body composition, serum lipids and dietary fat intake, and were genotyped for the IL-6 -174 G>C, IVS3 +281 G>T and IVS4 +869 A>G polymorphisms. In black women the IVS4 +869 G allele was associated with greater adiposity, and with increasing dietary fat intake adiposity increased in the IVS3 +281 GT+GG and IVS4 +869 AA or AG genotypes. In white women, with increasing omega-3 (n-3) intake and decreasing n-6:n-3 ratio, body mass index (BMI) decreased in those with the -174 C allele, IVS3 +281 T allele and IVS4 +869 AG genotype. In the white women, those with the IVS3 +281 T allele had lower triglycerides. Further, with increasing n-3 polyunsaturated fatty acid (PUFA); triglyceride and total cholesterol:high-density lipoprotein cholesterol (T-C:HDL-C) ratio decreased in those with the -174 C allele. In black women, with increasing total fat intake, triglycerides and T-C:HDL-C ratio increased in those with the IVS4 +869 G allele. This study is the first to show that dietary fat intake modulates the relationship between the IL-6 -174 G>C, IVS3 +281 G>T and IVS4 +869 A>G polymorphisms on obesity and serum lipids in black and white SA women.

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 distributions between control and tendinopathy groups for either the THBS2 variants rs9505888, rs6422747 and rs9283850, or the COMP variants rs730079 and rs28494505 in the SA and AUS populations. As the selection of COMP and THBS2 as candidate genes was hypothesis driven, based on biological function, the possibility that other variants within these genes are associated with Achilles tendinopathy cannot be excluded.

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, maintains homeostasis in the ECM by inhibiting ADAM, ADAMTS and MMP functions. We sought to determine whether single nucleotide polymorphisms (SNPs) within the ADAMTS2, ADAMTS5, ADAMTS14, ADAM12 and TIMP2 genes were associated with the risk of ATP in two independent populations., Design: 213 (115 ATP cases and 98 asymptomatic controls) South African Caucasian participants and 209 (60 ATP cases and 149 asymptomatic controls) Australian Caucasian participants were recruited for this case-control genetic association study., Methods: All participants were genotyped using TaqMan technology for the ADAMTS2 rs1054480, ADAMTS5 rs226794, ADAMTS14 rs4747096, ADAM12 rs3740199, and TIMP2 rs4789932 SNPs., Results: We report for the first time a significant (p=0.016) genotypic association between the TIMP2 rs4789932 variant and ATP in a combined Caucasian cohort. We also identify an interaction between the ADAMTS14 rs4747096 variant and age of onset of ATP (p=0.024)., Conclusions: Our data show that DNA sequence variation within the TIMP2 gene is a risk factor for ATP in Caucasians. Furthermore, carriage of the ADAMTS14 rs4747096 GG variant appears to delay onset of the injury in the ATP group., (Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Background: Type XI collagen, which is expressed in developing tendons and is encoded by the COL11A1, COL11A2 and COL2A1 genes, shares structural and functional homology with type V collagen, which plays an important role in collagen fibril assembly. We investigated the association of these three polymorphisms with Achilles tendinopathy (AT) and whether these polymorphisms interact with COL5A1 to modulate the risk of AT., Methods: 184 participants diagnosed with chronic AT (TEN) and 338 appropriately matched asymptomatic controls (CON) were genotyped for the three polymorphisms., Results: Although there were no independent associations with AT, the TCT pseudohaplotype constructed from rs3753841 (T/C), rs1676486 (C/T) and rs1799907 (T/A) was significantly over-represented (p=0.006) in the TEN (25.9%) compared with the CON (17.1%) group. The TCT(AGGG) pseudohaplotypes constructed using these type XI collagen polymorphisms and the functional COL5A1 rs71746744 (-/AGGG) polymorphism were also significantly over-represented (p<0.001) in the TEN (25.2%) compared with the CON (9.1%) group., Discussion: The genes encoding structural and functionally related type XI (COL11A1 and COL11A2) and type V (COL5A1) collagens interact with one another to collectively modulate the risk for AT. Although there are no immediate clinical applications, the results of this study provide additional evidence that interindividual variations in collagen fibril assembly might be an important molecular mechanism in the aetiology of chronic AT.

COL5A1 encodes for the α1 chain of type V collagen, an important regulator of fibril assembly in tendons, ligaments and other connective tissues. A polymorphism (rs12722) within the functional COL5A1 3'-untranslated region (UTR) has been shown to associate with chronic Achilles tendinopathy and other exercise-related phenotypes. The COL5A1 3'-UTR contains several putative cis-acting elements including a functional Hsa-miR-608 binding site. The aim of this study was to determine whether previously uncharacterized polymorphisms within a functional region of the COL5A1 3'-UTR or the MIR608 gene are associated with chronic Achilles tendinopathy. The effect of these COL5A1 3'-UTR polymorphisms on the 3'-UTR predicted mRNA secondary structure was also investigated. One hundred and sixty Caucasian chronic Achilles tendinopathic and 342 control participants were genotyped for the COL5A1 3'-UTR markers rs71746744, rs16399 and rs1134170, as well as marker rs4919510 within MIR608. All four genetic markers were independently associated with chronic Achilles tendinopathy. The COL5A1 polymorphisms appear to alter the predicted secondary structure of the 3'-UTR. We propose that the secondary structure plays a role in the regulation of the COL5A1 mRNA stability and by implication type V collagen production., (© 2013 Blackwell Publishing Ltd/University College London.)

The insertion allele of the angiotensin-converting enzyme (ACE) gene has been associated with endurance performance. Since a large portion of the variance seen in circulatory ACE levels is unaccounted for by the insertion/deletion polymorphism it is likely that the ACE phenotype would serve as a more informative marker in assessing elite endurance performance. The aim of this study was to correlate plasma ACE activity with performance of a homogenous population of South African-born Caucasian male triathletes. Plasma ACE activity was determined in 145 triathletes, representing the fastest and slowest subgroups who completed either the 2000 or 2001 South African Ironman Triathlon. There was a trend for lower mean plasma ACE activity in the fastest (28.85±8.60 mU/ml) when compared to the slowest finisher subgroup (31.65±8.75 mU/ml, P=0.055). There was a significant positive correlation between plasma ACE activity and overall finishing time within the participants who completed the event in under 15 h (r=0.192, P=0.029). There was also a positive correlation with cycle (r=0.195, P=0.034) and run (r=0.184, P=0.040) stages but not the swim stage (r=0.084, P=0.353). In conclusion, this is the first study to report a relationship between plasma ACE activity and endurance performance in humans., (© Georg Thieme Verlag KG Stuttgart · New York.)

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 implicates the genomic region containing the TNC and COL27A1 genes in influencing risk of AT, and maps the potential risk allele to a genetic interval flanked by rs946053 and rs2104772. This region may have functional effects on the transcription, structure and properties of tenascin-C and the alpha-1 chain of type XXVII collagen., (Copyright © 2012 Orthopaedic Research Society.)

Background/objectives: This study explored interactions between dietary fat intake and the tumor necrosis factor-α gene (TNFA) -238G>A polymorphism (rs361525) on adiposity and serum lipid concentrations in apparently healthy premenopausal black and white South African (SA) women., Subjects/methods: Normal-weight (N=107) and obese (N=120) black, and normal-weight (N=89) and obese (N=62) white SA women underwent measurements of body composition, fasting lipids and dietary intake, and were genotyped for the -238G>A polymorphism., Results: Black women had a higher -238GA genotype frequency than white women (P<0.001), but there were no differences between body mass index groups. Black women with the -238A allele had a greater body fat % than those with the GG genotype (P<0.001). Further, in black women, with increasing polyunsaturated:saturated fat ratio and omega-6 (n-6):omega-3 (n-3) ratio, high-density lipoprotein-cholesterol (HDL-C) concentrations decreased, and total cholesterol (T-C):HDL-C ratio increased in those with the GA genotype but not the GG genotype. In addition, with increasing n-3 polyunsaturated fatty acid intake (percentage of total energy intake, %E), T-C:HDL-C ratio decreased in those with the GA genotype, but not in those with the GG genotype. In white SA women, with increasing eicosapentaenoic acid (%E) intake, low-density lipoprotein-cholesterol concentrations decreased in those with the GG genotype but not the GA genotype., Conclusions: The -238G>A polymorphism was associated with body fatness in black women. Interactions between -238G>A genotypes and dietary fat intake on serum lipids and adiposity differed depending on dietary fat intake, but those for serum lipids were not the same in black and white SA women.

The arginine vasopressin receptor 2 (AVPR2) plays an important antidiuretic role in regulating water balance to maintain osmotic equilibrium. The aim of this study was to determine if there were any associations between single nucleotide polymorphisms (SNPs), within the AVPR2 gene, and changes in serum sodium concentrations and/or body weight (BW) in Ironman triathletes. Caucasian male triathletes who completed either the 2000, 2001 or 2006 South African Ironman Triathlons were genotyped (n=570) for at least one SNP. Pre- and post-race serum [Na+] (pre n=514; post n=423) and BWs (pre n=556; post n=552) were measured. Triathletes were divided into 3 groups according to their relative BW loss during the triathlon (BW loss of 0-3, 3-5 and >5%). There was a significant linear trend (p=0.010, x2=6.7) for the distribution of minor haplotypes GCT, GTC and GCC across the 3 BW loss groups. The >5% group had the highest percentage (4.7%) of triathletes with minor haplotypes followed by the 3-5% (3.6%) and 3-0% (0%) groups. In conclusion, the minor haplotype constructs of AVPR2 SNPs were associated with larger BW losses during the Ironman Triathlons. This finding supports a possible genetic contribution to BW loss during endurance exercise events acting through the argine vasopression system., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Running economy, a key component of endurance ability, has been shown to be associated with flexibility. Increased stiffness (inflexibility) may improve running economy and therefore endurance running ability. The COL5A1 gene, which encodes the α1-chain of type V collagen, was found to associate with measures of flexibility. Type V collagen is a quantitatively minor fibrillar collagen, which is believed to regulate fibrillogenesis within tendons and other connective tissue., Purpose: The aim of this study was therefore to determine whether the COL5A1 gene is associated with endurance performance., Methods: Three hundred thirteen Caucasian male participants who completed either the 2006 or the 2007 226-km South African Ironman triathlon (3.8-km swim, 180-km bike, and 42.2-km run) participated in this study. All participants were genotyped for the COL5A1 BstUI restriction fragment length polymorphism (RFLP)., Results: The COL5A1 BstUI RFLP was significantly associated with time to complete the running component of the triathlon. Participants with a TT genotype completed the running component of the race significantly faster than individuals with a CC genotype (P = 0.019; mean ± SD: TT = 294.2 ± 52.1 min, CC = 307.4 ± 48.6 min). In addition, there was a significant linear trend (P = 0.020) in the CC genotype distribution when the run times were divided into the fastest (13%), middle (17%), and slowest (25%) tertiles. There were no significant genotype differences for time to complete the swim, the bike, or the overall race. COL5A1 BstUI RFLP, body mass index, age, and 15 wk of running training history predicted 30% of the variance in running performance., Conclusion: This is the first study to identify the COL5A1 BstUI RFLP as a marker for endurance running performance. Further studies are required to replicate these findings.

Objectives: Achilles tendon pathology is a multifactorial condition for which various risk factors, including genetic factors, have been identified. Gene transfection of two members of the TGF-β family, TGF-β1 and growth/differentiation factor-5 (GDF-5), have been shown to enhance tendon repair and mechanical strength within animal Achilles tendon injury models. The objective of this study was to investigate whether two functional 5' untranslated region (UTR) single nucleotide polymorphisms (SNPs), the TGFB1 rs1800469 variant and the GDF5 rs143383 variant, were associated with ATP within an Australian ('AUS') and a South African ('SA') case-control cohort., Methods: One hundred and seventy-one subjects (58 AUS and 112 SA) with Achilles tendon pathology (ATP group) and 235 (142 AUS and 96 SA) asymptomatic control (CON group) subjects were genotyped for the selected SNPs using custom-designed Taqman assays. A χ(2)-analysis or Fisher's exact test was used to analyse any differences in the genotype and allele frequencies. Significance was accepted when P < 0.05., Results: There were no significant TGFB1 rs1800469 genotype (P = 0.491) or allele (P = 0.400) frequency differences between the ATP and CON groups. The TT genotype of the GDF5 rs143383 variant was significantly over-represented in the ATP group of the AUS cohort [P = 0.011; odds ratio (OR) = 2.24; 95% CI 1.21, 4.16], and when the AUS and SA cohorts were combined (P = 0.004; OR = 1.82; 95% CI 1.23, 2.74)., Conclusions: In conclusion, this study suggests that individuals with a TT genotype of the functional GDF5 rs143383 variant have twice the risk of developing ATP. This finding highlights a role of GDF-5 in the pathogenesis of Achilles tendon pathology.

The prevalence of obesity and related disease risk is high in black South African (SA) women, possibly influenced by the dietary transition associated with urbanization. This study explored interactions between dietary fat intake and the tumor necrosis factor-alpha (TNFA) -308 G/A polymorphism on obesity, insulin resistance, and serum lipid concentrations in urbanized black SA women. Normal-weight (n = 105) and obese (n = 118) women underwent measurements of body composition, fat distribution, fasting serum lipids, glucose and insulin concentrations, and dietary intake. Participants were genotyped for the functional TNFA -308 G/A polymorphism. The genotype or allele frequency of the TNFA -308 G/A polymorphism did not differ between the BMI groups. However, when dietary fat intake was 30% of total energy intake [percentage energy (%E)], the odds of being obese with the TNFA GA+AA genotype was only 12% of that with GG, but increasing intake of dietary fat (%E) was associated with a significantly faster rate of increase in obesity risk in women with the TNFA GA+AA genotype compared with those with the GG genotype (P = 0.036). There were significant diet-gene interactions between alpha-linolenic acid (%E) and the total cholesterol:HDL-cholesterol ratio (P = 0.036), and PUFA (%E) and LDL cholesterol levels (P = 0.026), with participants with the A allele being more responsive to changes in relative fat intake. The TNFA -308 G/A polymorphism modified the relationship between dietary fat intake, obesity risk, and serum lipid concentrations in black SA women.

The aim of the present study was to compare body fat percent (BF %) using single-site near-IR reactance (NIR) and dual-energy X-ray absorptiometry (DXA) in a cohort of normal-weight (BMI < 25 kg/m2) black (n 102) and white (n 71); and obese (BMI > or = 30 kg/m2) black (n 117) and white (n 41) South African women (18-45 years). NIR-derived BF % was significantly correlated with DXA-derived BF % in all groups: normal-weight black (r 0.55, 95 % CI: 0.40, 0.67, P < 0.001) and white (r 0.69, 95 % CI: 0.53, 0.79, P < 0.001) women; obese black (r 0.59, 95 % CI: 0.46, 0.70, P < 0.001) and white (r 0.56, 95 % CI: 0.30, 0.74, P < 0.001) women. NIR under-predicted BF% compared to DXA in black women (normal-weight, - 4.36 (sd 4.13) % and obese, - 3.41 (sd 3.72) %), while smaller mean differences were observed in white women (normal-weight, - 0.29 (sd 4.19) % and obese, - 0.81 (sd 3.09) %), irrespective of normal-weight or obese status (P < 0.001). In obese subjects, NIR-derived BF % did not measure values greater than approximately 45 %, while the maximum DXA-derived measure was 58 %. In conclusion, although there was a significant relationship between NIR- and DXA-derived BF %, NIR under-predicted BF % in normal-weight and obese black South African women compared to DXA, but to a greater extent in subjects with very high levels of adiposity (>45 %). The results of single-site NIR as a measure of BF % should therefore be interpreted with caution, particularly in women of African descent and in those with very high levels of adiposity.

There is an interest in identifying the intrinsic risk factors, including altered musculotendinous flexibility, that may be associated with musculotendinous injuries. We have recently shown that a sequence variant, namely the BstUI restriction fragment length polymorphism (RFLP), within the COL5A1 gene is associated with chronic Achilles tendinopathy. Mutations within COL5A1 have been implicated in Ehlers Danlos syndrome, a condition that is characterized by joint hypermobility. The aim of this study was to investigate the association of sequence variants within COL5A1 and musculotendinous range of motion (ROM). The sit and reach (SR) and the passive straight leg raise (SLR) were measured on 119 Caucasian subjects with either a past, current or no history of Achilles tendon injuries. The subjects were genotyped for four sequence variants within the 3'-UTR of the COL5A1 gene. Gender (P=0.016), age (P=0.011) and the BstUI RFLP (P=0.010) jointly contributed significantly to the optimal SLR model which accounted for 19.3% of the variance. The factors contributing significantly to SR, which accounted for 28.8% of the variance, were weight (P=0.004), age (P<0.001) and the BstUI RFLP (P=0.001). These data suggest that the COL5A1 BstUI RFLP is independently associated with lower limb ROM within the cohort investigated in this study.

Previous studies have identified an association of genetic variants believed to alter physiological and biochemical processes locally within the skeletal muscle and therefore performance in the Ironman triathlon. There is growing evidence that the serotonergic system and circulating interleukin (IL)-6 levels are also involved in mediating endurance capacity. Investigators have demonstrated that recombinant human IL-6 administration and serotonergic neurotransmission manipulation, with 5-hydroxytryptamine transporter (5-HTT) and monoamine oxidase A (MAO-A) inhibitors, prior to exercise, can alter running performance, consistent with a central governor hypothesis. The aim of this study was to investigate possible associations of functional polymorphisms within the IL-6, 5-HTT, and MAO-A genes with endurance performance of Ironman triathletes. Four hundred sixty-eight male Caucasian triathletes who completed the 2000 and (or) 2001 South African Ironman Triathlon and 200 healthy Caucasian male controls were genotyped for the -174 IL-6 G/C, 5-HTT 40 base pair (bp) insertion-deletion and 30 bp variable number of tandem repeats (VNTR) MAO-A gene polymorphisms. There were no significant differences in the relative genotype distributions within the IL-6 (p = 0.636), 5-HTT (p = 0.659), and MOA-A (p = 0.227) polymorphisms when the fastest-fnishing, middle-finishing, and slowest-finishing triathletes, as well as the control groups, were compared. There were no direct associations between the IL-6 -174 G/C, 5-HTT 44 bp insertion-deletion, and MAO-A 30 bp VNTR gene polymorphisms and endurance performance in the 2000 and (or) 2001 South African Ironman Triathlons. The neurogenetic basis of the central governor requires further investigation.

The objective of the study was to examine the association between a functional 4 bp proinsulin gene insertion polymorphism (IVS-69), fasting insulin concentrations, and body composition in black South African women. Body composition, body fat distribution, fasting glucose and insulin concentrations, and IVS-69 genotype were measured in 115 normal-weight (BMI<25 kg/m2) and 138 obese (BMI>or=30 kg/m2) premenopausal women. The frequency of the insertion allele was significantly higher in the class 2 obese (BMI>or=35 kg/m2) compared with the normal-weight group (P=0.029). Obese subjects with the insertion allele had greater fat mass (42.3+/-0.9 vs. 38.9+/-0.9 kg, P=0.034) and fat-free soft tissue mass (47.4+/-0.6 vs. 45.1+/-0.6 kg, P=0.014), and more abdominal subcutaneous adipose tissue (SAT, 595+/-17 vs. 531+/-17 cm2, P=0.025) but not visceral fat (P=0.739), than obese homozygotes for the wild-type allele. Only SAT was greater in normal-weight subjects with the insertion allele (P=0.048). There were no differences in fasting insulin or glucose levels between subjects with the insertion allele or homozygotes for the wild-type allele in the normal-weight or obese groups. In conclusion, the 4 bp proinsulin gene insertion allele is associated with extreme obesity, reflected by greater fat-free soft tissue mass and fat mass, particularly SAT, in obese black South African women.

Objective: The purpose of this study was to characterize differences in the acute insulin response to glucose (AIR(g)) relative to insulin sensitivity (S(I)) in black and white premenopausal normoglycemic South African women matched for body fatness., Research Design and Methods: Cross-sectional analysis including 57 black and white South African women matched for BMI, S(I), AIR(g), and the disposition index (AIR(g) x S(I)) were performed using a frequently sampled intravenous glucose tolerance test with minimal model analysis, and similar measures were analyzed using an oral glucose tolerance test (OGTT). Body composition was assessed by dual-energy X-ray absorptiometry and computed tomography., Results: S(I) was significantly lower (4.4 +/- 0.8 vs. 9.4 +/- 0.8 and 2.9 +/- 0.8 vs. 6.0 +/- 0. 8 x 10(-5) min(-1)/[pmol/l], P < 0.001) and AIR(g) was significantly higher (1,028 +/- 255 vs. 352 +/- 246 and 1,968 +/- 229 vs. 469 +/- 246 pmol/l, P < 0.001), despite similar body fatness (30.9 +/- 1.4 vs. 29.7 +/- 1.3 and 46.8 +/- 1.2 vs. 44.4 +/- 1.3%) in the normal-weight and obese black women compared with their white counterparts, respectively. Disposition index, a marker of beta-cell function, was not different between ethnic groups (3,811 +/- 538 vs. 2,966 +/- 518 and 3,646 +/- 485 vs. 2,353 +/- 518 x 10(-5) min, P = 0.10). Similar results were obtained for the OGTT-derived measures., Conclusions: Black South African women are more insulin resistant than their white counterparts but compensate by increasing their insulin response to maintain normal glucose levels, suggesting an appropriate beta-cell response for the level of insulin sensitivity.

Objectives: 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., Methods: 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., Results: The BstUI RFLP (p<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., Conclusion: The BstUI RFLP is associated with chronic Achilles tendinopathy in a second population and a region within the COL5A1 3' untranslated region may predispose individuals to an increased risk of developing chronic Achilles tendinopathy.

The superior performance of black African runners has been associated with lower plasma lactate concentrations at sub-maximal intensities compared to white runners. The aim was to investigate the monocarboxylate transporters 1 (MCT1) and MCT4 content in skeletal muscle of black and white runners. Although black runners exhibited lower plasma lactate concentrations after maximum exercise (8.8 +/- 2.0 vs. 12.3 +/- 2.7 mmol l(-1), P < 0.05) and a tendency to be lower at 16 km h(-1) (2.4 +/- 0.7 vs. 3.8 +/- 2.4 mmol l(-1), P = 0.07) than the white runners, there were no differences in MCT1 or MCT4 levels between the two groups. For black and white runners together, MCT4 content correlated significantly with 10 km personal best time (r = -0.74, P < 0.01) and peak treadmill speed (r = 0.88, P < 0.001), but MCT1 content did not. Although whole homogenate MCT content was not different between the groups, more research is required to explain the lower plasma lactate concentrations in black runners.

The appropriateness of the metabolic syndrome criteria as an indicator of cardiovascular disease risk has been challenged in black Africans. Hence, the aims of this study were (1) to examine the level of agreement between the International Diabetes Federation (IDF) and the National Cholesterol Education Program Adult Treatment Panel III (ATP III) metabolic syndrome criteria, which differ in their emphasis on central obesity; (2) to investigate the degree to which these criteria predict insulin resistance, as estimated by the homeostasis model assessment of insulin resistance (HOMA-IR); and (3) to investigate the extent to which a diagnosis of the metabolic syndrome and insulin resistance may be explained by body fat and its distribution. In 103 normal-weight (body mass index or=30 kg/m(2), mean: 33.9 +/- 5.5 kg/m(2)) urbanized black South African women (27 +/- 7 years old), body composition (dual-energy x-ray absorptiometry), fat distribution (waist and computed tomography), blood pressure, fasting glucose, HOMA-IR, and lipid profiles were measured. Insulin resistance was defined as the upper tertile of HOMA-IR. The overall proportion of individuals who met the IDF and ATP III metabolic syndrome criteria were 13% and 10%, respectively. Agreement was high between the IDF and ATP III metabolic syndrome criteria (kappa = 0.87); however, neither criteria predicted HOMA-IR (kappa = 0.16, 95% confidence interval: 0.05-0.27 and 0.14, 95% confidence interval: 0.05-0.27, respectively). Visceral adipose tissue was the largest contributor to diagnosis of the metabolic syndrome, and waist alone (>80 cm or >88 cm) had an improved specificity (21% or 18% higher, respectively) and positive predictive value (64% or 57% higher, respectively) for identifying insulin resistance compared with the metabolic syndrome criteria. Waist circumference was a better predictor of HOMA-IR than the IDF or ATP III metabolic syndrome criteria in young black African women without known disease. The measurement of waist circumference, as an indicator of disease risk, should therefore be encouraged in the public health setting.

Sequence variants within the type V collagen (COL5A1) and tenascin C (TNC) genes have to date been shown to be associated with chronic Achilles tendinopathies and/or spontaneous Achilles tendon ruptures. Type V collagen and tenascin C are quantitatively minor components of tendon, while type I collagen is the major structural component. There is increased expression of the COL1A1 gene, which encodes for the alpha1 chain of type I collagen, in the painful Achilles tendon. A functional Sp1-binding site polymorphism (SNP rs1800012; IVS1+1023G>T) within this gene has been shown to be associated with several connective tissue disorders. The aim of this study was to determine whether the Sp1-binding site polymorphism within the COL1A1 gene is associated with chronic Achilles tendinopathies and/or spontaneous Achilles tendon ruptures. Achilles tendinopathy (n=85), Achilles rupture (n=41) and asymptomatic control (n=125) participants were genotyped for the COL1A1 Sp1-binding site polymorphism. There were no observed statistical differences in the genotype (p=0.602) or allele (p=0.694) distributions between the groups. In conclusion, this study has shown that there is no association between the Sp1-binding site polymorphism within the first intron of COL1A1 and Achilles tendinopathy or Achilles tendon rupture within the population studied.

Objective: Subsets of metabolically "healthy obese" and "at-risk" normal-weight individuals have been previously identified. The aim of this study was to explore the determinants of these phenotypes in black South African (SA) women., Methods and Procedures: From a total of 103 normal-weight (BMI or= 30 kg/m(2)) black SA women, body composition, fat distribution, blood pressure, fasting glucose levels, insulin resistance, and lipid profiles were measured. Questionnaires relating to family history, physical activity energy expenditure (PAEE), and socio-demographic variables were administered. The subjects were classified as insulin sensitive or insulin resistant according to the homeostasis model assessment of insulin resistance (HOMA-IR) (>or=1.95 insulin resistant)., Results: Our study showed that 22% of the normal-weight women were insulin resistant and 38% of the obese women were insulin sensitive. Increased visceral adipose tissue (VAT) (P=0.001) and decreased VAT/leg fat mass (P

Alpha-actinins are major structural components of the Z-discs in skeletal muscle. Alpha-actinin 3 is encoded by the ACTN3 gene and is expressed only in type II muscle fibres. Homozygosity for the nonsense mutation, 577X, within ACTN3 results in deficiency of alpha-actinin-3 but does not result in an abnormal muscular phenotype. Previous research has found an association of the 577R allele with sprinting and/or power performance. It has also been suggested that the 577X allele may confer an advantage during endurance events. Four hundred and fifty seven Caucasian male triathletes who completed either the 2000 and/or 2001 226 km South African Ironman Triathlons, and 143 Caucasian controls, were genotyped for the R577X mutation within the ACTN3 gene. There were no significant differences in either the genotype (P = 0.486) or allele (P = 0.375) frequencies within the fastest, middle of the field or slowest Caucasian male finishers and the control population. In conclusion, the R577X polymorphism within the ACTN3 gene was not associated with ultra-endurance performance in the 2000 and 2001 South African Ironman Triathlons.

Objective: To assess (1) the incidence of dysnatremia in collapsed runners presenting to the medical tent of the 89-km Comrades Marathon and whether dysnatremia influences time to discharge, and (2) whether intravenous fluids could restore serum sodium concentration ([Na+]) to 140 mM faster than could the administration of oral fluids., Design: Prospective randomized controlled trial., Setting: 2005 Comrades Marathon., Participants: One hundred thirty-three collapsed runners and 31 control-group runners., Interventions: Collapsed runners presenting to the medical tent at the finish of the 2005 Comrades Marathon were randomized into an intravenous or oral fluid administration group, with the type and amount of fluid administered dictated by initial [Na+]., Main Outcome Measures: Time to discharge, serum [Na+]., Results: Forty-five percent of collapsed runners were hypernatremic, 2% were hyponatremic, and 53% were normonatremic. Normonatremic runners spent significantly less time in the medical tent (80 +/- 31 minutes) compared with hypernatremic (102 +/- 36 minutes) and hyponatremic (146 +/- 122 minutes) runners. Intravenous fluid therapy produced larger but nonsignificant reductions in [Na+] than oral therapy (-2.1 +/- 3.1 versus -0.7 +/- 1.8 mM); however, 45% of runners assigned to the oral fluid group could not tolerate oral rehydration., Conclusions: A slight majority of collapsed runners were normonatremic and spent significantly less time in the medical tent compared with hyper- and hyponatremic athletes. Initial rates of correction of hypernatremia were similar with intravenous and oral hypotonic fluid therapy. Clinicians should be advised that intravenous fluid resuscitation may best benefit hypernatremic collapsed runners who are intolerant to oral fluid ingestion.

Thirst is regulated by a complex interaction of signalling pathways within the central nervous system, including components of the renin-angiotensin and kalikrein kinin systems, as well as the serotonergic pathways. The aim of this study was to determine whether there were any associations between polymorphisms within the ACE, BDKRB2, NOS3 and/or 5-HTT genes with weight changes during the 2000 and 2001 226 km South African Ironman Triathlons. Pre- and post-race serum [Na(+)] and body weights, as well as genotype data, were collected from 428 (61.1%) Caucasian male triathletes who were divided into three groups according to their relative weight loss during the triathlon (0-3, 3-5 and >5%). There was a significant linear trend for the distribution of both the BDKRB2 +9/+9 genotype and the 5-HTT SS genotype between the three weight loss groups, with the >5% group having the highest percentage of athletes with the +9/+9 genotype (chi(2)=5.3, P=0.021) and the highest percentage of athletes with the SS genotype (chi(2)=5.8, P=0.016). Likewise, the >5% group had the highest percentage of athletes with the combined SS 5-HTT and/or +9/+9 BDKRB2 genotypes (chi(2)=7.4, P=0.007). In conclusion, the functional SS genotype of the serotonin transporter-linked polymorphic region (5-HTTLPR) within the 5-HTT gene and the functional +9/+9 genotype of the BDKBR2 gene were associated with larger weight losses during the Ironman Triathlons. These findings suggest the involvement of the serotonergic pathways in the control of thirst and drinking behaviour and provide further evidence for the dipsogenic effect of circulating bradykinin.

We have previously shown that the insertion allele of the angiotensin-converting enzyme (ACE) gene was over-represented in the fastest South-African-born finishers of the South African Ironman Triathlons. As ACE is a component of the skeletal muscle kallikrein-kinin system (KKS), the aim of this study is to determine if there are any further associations between polymorphisms within the BDKRB2 and NOS3 genes, which encode for the KKS components, bradykinin beta(2) receptor and nitric oxide synthase, respectively, and ultra-endurance performance during the Ironman Triathlons. Four-hundred and forty-three male Caucasian triathletes who completed the 2000 and/or 2001 South African Ironman Triathlons and 203 healthy Caucasian male control subjects were genotyped for the functional -9/+9 polymorphism within exon 1 of the BDKRB2 gene and the G894T NOS3 gene polymorphisms. The BDKRB2 -9/-9 genotype occurred at a significantly higher frequency when the triathlete group (27.0%) was compared with the control group (19.3%, P=0.035). When divided into tertiles, there was also a significant linear trend for the NOS3 GG genotype distribution among the fastest (35.0%), middle (40.4%) and slowest (46.9%) finishers (P=0.039). The overall finishing times of the triathletes with an NOS3 GG genotype together with a BDKRB2 +9 allele were significantly slower than those with other genotype combinations (P=0.001). The NOS3/BDKRB2 genotype (beta=-0.150, B=-31.48, P=0.002), together with body mass index and age, accounted for 14.6% of the variance in the overall race time for the triathlon. In conclusion, both the NOS3 and BDKRB2 genes are associated with the actual performance during the Ironman Triathlons.

Context: Critical assessment of recommendations that athletes consume additional sodium during athletic events., Objective: To evaluate if sodium supplementation is necessary to maintain serum sodium concentrations during prolonged endurance activity and prevent the development of hyponatraemia., Design: Prospective randomised trial of athletes receiving sodium (620 mg table salt), placebo (596 mg starch), or no supplementation during a triathlon. The sodium and placebo tablets were taken ad libitum, with the suggested range of 1-4 per hour., Setting: The 2001 Cape Town Ironman triathlon (3.8 km swim, 180 km cycle, 42.2 km run)., Subjects: A total of 413 triathletes completing the Ironman race., Main Outcome Measures: Sodium supplementation was not necessary to maintain serum sodium concentrations in athletes completing an Ironman triathlon nor required to prevent hyponatraemia from occurring in athletes who did not ingest supplemental sodium during the race., Results: Subjects in the sodium supplementation group ingested an additional 3.6 (2.0) g (156 (88) mmol) sodium during the race (all values are mean (SD)). There were no significant differences between the sodium, placebo, and no supplementation groups with regard to age, finishing time, serum sodium concentration before and after the race, weight before the race, weight change during the race, and rectal temperature, systolic and diastolic blood pressure after the race. The sodium supplementation group consumed 14.7 (8.3) tablets, and the placebo group took 15.8 (10.1) tablets (p = 0.55; NS)., Conclusions: Ad libitum sodium supplementation was not necessary to preserve serum sodium concentrations in athletes competing for about 12 hours in an Ironman triathlon. The Institute of Medicine's recommended daily adequate intake of sodium (1.5 g/65 mmol) seems sufficient for a healthy person without further need to supplement during athletic activity.

Background: Some studies have suggested that the insertion allele of the ACE gene is associated with endurance performance, including the Ironman triathlon. It is possible that this association is due to genetic linkage between the ACE I/D locus and the T/A variant in intron 4 of the neighbouring GH1 gene. The A variant is associated with lower levels of growth hormone production. Growth hormone has multiple effects, especially on metabolism during exercise and recovery from exercise. Its production during exercise has also been shown to stimulate sweat rate and heat loss., Objective: To determine whether the GH1 gene is associated with the performance and/or post-race rectal temperatures of competitors in the South African Ironman triathlon., Methods: A total of 169 of the fastest finishing white male triathletes who completed the 2000 and/or 2001 South African Ironman triathlon and 155 control subjects were genotyped for the T/A variant in the GH1 gene. Post-race rectal temperature was also determined in 103 of these triathletes., Results: There was no significant difference in the frequency of this polymorphism in the GH1 gene when the fastest finishing triathletes were compared with the control subjects. Post-race rectal temperatures were, however, significantly higher in those triathletes with an AA genotype (mean (SD) 37.7 (0.8) degrees C) compared with those with a TT genotype (37.2 (0.8) degrees C) (p = 0.019)., Conclusions: The T/A polymorphism in intron 4 of the GH1 gene was not associated with performance of the fastest finishers of the South African Ironman triathlon. Post-race rectal temperatures were, however, significantly higher in the fastest finishing athletes, who were homozygous for a GH1 genotype associated with lower growth hormone production.

Uncoupling protein 3 is believed to be involved in total body energy expenditure, including the regulation of fat and glucose metabolism. These biochemical processes may distinguish top ultra-endurance triathletes from slower competitors. The aim of this study was to determine whether the uncoupling protein 3 gene is associated with the performance capacity of ultra-endurance Ironman triathletes. Two triathlete groups consisting of the 89 fastest and 89 slowest Caucasian, male triathletes who completed either the 2000 or 2001 South African Ironman triathlon events were genotyped for the -55 C/T polymorphism within the uncoupling protein 3 gene. A control group consisting of 92 Caucasian males who had not trained for or participated in an ultra-endurance athletic event was also genotyped. There was no significant difference in the genotype (CC, CT and TT) frequency distribution of the -55 C/T polymorphism within the uncoupling protein 3 gene between the fast triathlete, slow triathlete and control groups. In addition, no significant differences were observed between the frequencies of the C and T alleles between the three groups. The two triathlete groups were combined and grouped according to their genotype. No particular genotype or allele was associated with the time taken by the triathletes to complete the entire triathlon, or either the swim, cycle or run legs of the event. Thus no association was found between the -55 C/T polymorphism within the uncoupling protein 3 gene and the ultra-endurance performance of triathletes who completed either the 2000 or 2001 South African Ironman triathlons.

Purpose: Several studies have suggested that the insertion (I) variant rather than the deletion (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with elite endurance performance. The aim of this study was to determine whether the ID polymorphism is associated with the performance of the fastest finishers of the South African Ironman Triathlons., Methods: A total of 447 Caucasian male triathletes of a variety of nationalities and athletic ability who completed either the 2000 or 2001 South African Ironman Triathlons and 199 Caucasian male control subjects were genotyped for the ACE ID polymorphism., Results: There was a significantly higher frequency of the I allele in the fastest 100 South African-born finishers (103 I, 51.5% and 97 D, 48.5%) compared with the 166 South African-born control subjects (140 I, 42.2% and 192 D, 57.8%) (P = 0.036). There was also a significant linear trend for the allele distribution among the fastest 100 finishers (I allele = 51.5%), slowest 100 finishers (I allele = 47.5%), and control (I allele = 42.2%) South African-born subjects (P = 0.033). There was, however, no significant difference in the ACE genotype or allele frequencies when athletes born outside South Africa were analyzed., Conclusion: To our knowledge this is the first study that has examined the effect of an athlete's ACE genotype on their actual performance during an ultra-endurance race. The I allele of the ACE gene was associated with the endurance performance of the fastest 100 South African-born finishers in these triathlons.

Objective: To establish relationships between body weight changes and serum sodium during and after an Ironman Triathlon, and postrace fluid status and rectal temperature, including the incidence of hyponatremia., Design: Descriptive research., Setting: The 2000 South African Ironman Triathlon, in which each athlete swam 3.8 km, cycled 180 km, and ran 42.2 km., Participants: All entrants in the race were invited to participate in the study., Methods: Athletes were weighed at registration, immediately prerace, immediately postrace, and 12 hours later. Blood samples were drawn at registration and immediately postrace. Rectal temperatures were measured postrace., Results: Starting body weight was significantly related to total finishing time (r = 0.27) and to cycling (r = 0.20) and running (r = 0.28) time. Body weight decreased significantly (p < 0.0001) during the race and had not returned to prerace values 12 hours later (p < 0.0001). Percentage change in body weight was unrelated to postrace rectal temperatures and inversely related to the postrace serum sodium concentrations (r = -0.45). Postrace serum sodium concentrations fell within a normal distribution (141.8 +/- 3.1 mmol.L(-1), mean +/- SD) and were negatively correlated to overall triathlon time (r = -0.22). Three sodium values (0.6%) were below 135 mmol.L(-1). Percentage change in body weight was unrelated to time in the marathon leg., Conclusions: Percentage change in body weight was linearly related to postrace serum sodium concentrations but unrelated to postrace rectal temperature or performance in the marathon. There was no evidence that in this study, more severe levels of weight loss or dehydration were related to either higher body temperatures or impaired performance.