Genetics of skeletal muscle strength and its determinants in healthy, untrained males

It is well accepted that inter-individual variability exists in muscle strength (more specifically maximal voluntary contraction torque), and many of its determinants. The extent of this inter-individual variability, however, has yet to be quantified despite many researchers suggesting genetic factors contribute. The aims of the present thesis were to first quantify the inter-individual variability within skeletal muscle phenotypes in a homogenous population, and secondly to investigate the contribution of multiple genetic polymorphisms to the inter-individual variability within these phenotypes. Genotype and phenotype data was collected from 120 untrained Caucasian males (aged 18-39 yr). Considerable inter-individual variability in muscle strength phenotypes and many of its determinants was observed. Subsequently, polymorphisms in the CNTF, TTN, PTK2, TRHR and ACTN3 genes demonstrated significant associations with one or more of the skeletal muscle phenotypes, but neither ACE nor COL5A1 were found to associate with any of the measured phenotypes. Adopting a polygenic approach that incorporated all of these genetic polymorphisms did not account for the inter-individual variability observed within VL muscle size (inter-individual variability = 13-20%; P ≥ 0.166) or strength (14-19%; P ≥ 0.220). The results identified novel genetic associations between TTN, CNTF and skeletal muscle architecture, in addition to providing the first independent replications of associations between PTK2 and specific force, and TRHR and lean mass. In conclusion, there appears to be a genetic influence on skeletal muscle phenotypes, however, further research is necessary to replicate the associations observed within the current thesis in comparable and different populations. Nonetheless, the work presented here has applications for improving physical performance, in addition to enhancing our understanding of skeletal muscle disorders, which may have implications for how individuals exercise and how skeletal muscle disorders are treated and/or prevented in future

Effects of the menstrual cycle phase on anterior cruciate ligament neuromuscular and biomechanical injury risk surrogates in eumenorrheic and naturally menstruating women: a systematic review

Background Eumenorrheic women experience cyclic variations in sex hormones attributed to the menstrual cycle (MC) which can impact anterior cruciate ligament (ACL) properties, knee laxity, and neuromuscular function. This systematic review aimed to examine the effects of the MC on ACL neuromuscular and biomechanical injury risk surrogates during dynamic tasks, to establish whether a particular MC phase predisposes women to greater ACL injury risk. Methods PubMed, Medline, SPORTDiscus, and Web of Science were searched (May-July 2021) for studies that investigated the effects of the MC on ACL neuromuscular and biomechanical injury risk surrogates. Inclusion criteria were: 1) injury-free women (18–40 years); 2) verified MC phases via biochemical analysis and/or ovulation kits; 3) examined neuromuscular and/or biomechanical injury risk surrogates during dynamic tasks; 4) compared ≥1 outcome measure across ≥2 defined MC phases. Results Seven of 418 articles were included. Four studies reported no significant differences in ACL injury risk surrogates between MC phases. Two studies showed evidence the mid-luteal phase may predispose women to greater risk of non-contact ACL injury. Three studies reported knee laxity fluctuated across the MC; two of which demonstrated MC attributed changes in knee laxity were associated with changes in knee joint loading (KJL). Study quality (Modified Downs and Black Checklist score: 7–9) and quality of evidence were low to very low (Grading of Recommendations Assessment Development and Evaluation: very low). Conclusion It is inconclusive whether a particular MC phase predisposes women to greater non-contact ACL injury risk based on neuromuscular and biomechanical surrogates. Practitioners should be cautious manipulating their physical preparation, injury mitigation, and screening practises based on current evidence. Although variable (i.e., magnitude and direction), MC attributed changes in knee laxity were associated with changes in potentially hazardous KJLs. Monitoring knee laxity could therefore be a viable strategy to infer possible ACL injury risk

Anthropometric and Physiological Characteristics of Elite Male Rugby Athletes

This is the first article to review the anthropometric and physiological characteristics required for elite rugby performance within both Rugby Union (RU) and Rugby League (RL). Anthropometric characteristics such as height and mass, and physiological characteristics such as speed and muscular strength, have previously been advocated as key discriminators of playing level within rugby. This review aimed to identify the key anthropometric and physiological properties required for elite performance in rugby, distinguishing between RU and RL, forwards and backs and competitive levels. There are differences between competitive standards such that, at the elite level, athletes are heaviest (RU forwards ~111 kg, backs ~93 kg; RL forwards ~103 kg, backs ~90 kg) with lowest % body fat (RU forwards ~15%, backs ~12%; RL forwards ~14%, backs ~11%), they have most fat-free mass and are strongest (Back squat: RU forwards ~176 kg, backs ~157 kg; RL forwards ~188 kg, backs ~ 168 kg; Bench press: RU forwards ~131 kg, backs ~118 kg; RL forwards ~122 kg, backs ~113 kg) and fastest (10 m: RU forwards ~1.87 s, backs ~1.77 s; 10 m RL forwards ~1.9 s, backs ~1.83 s). We also have unpublished data that indicate contemporary RU athletes have less body fat and are stronger and faster than the published data suggest. Regardless, well-developed speed, agility, lower-body power and strength characteristics are vital for elite performance, probably reflect both environmental (training, diet, etc.) and genetic factors, distinguish between competitive levels and are therefore important determinants of elite status in rugby.Published versio

12-Month changes of muscle strength, body composition and physical activity in adults with dystrophinopathies

Purpose Muscular dystrophy (MD) is an umbrella term for muscle wasting conditions, for which longitudinal changes in function and body composition are well established in children with Duchenne (DMD), however, changes in adults with DMD and Beckers (BMD), respectively, remain poorly reported. This study aims to assess 12-month changes in lower-limb strength, muscle size, body composition and physical activity in adults with Muscular Dystrophy (MD). Methods Adult males with Duchenne MD (DMD; N = 15) and Beckers MD (BMD; N = 12) were assessed at baseline and 12-months for body composition (Body fat and lean body mass (LBM)), Isometric maximal voluntary contraction (Knee-Extension (KEMVC) and Plantar-Flexion (PFMVC)) and physical activity (tri-axial accelerometry). Results 12-Month change in strength was found as −19% (PFMVC) and −14% (KEMVC) in DMD. 12-Month change in strength in BMD, although non-significant, was explained by physical activity (R 2=0.532–0.585). Changes in LBM (DMD) and body fat (BMD) were both masked by non-significant changes in body mass. Discussion 12-Month changes in adults with DMD appear consistent with paediatric populations. Physical activity appears important for muscle function maintenance. Specific monitoring of body composition, and potential co-morbidities, within adults with MD is highlighted. Implications for rehabilitation Quantitative muscle strength assessment shows progressive muscle weakness in adults with Duchenne Muscular Dystrophy is comparable to paediatric reports (−14 to −19%). Physical activity should be encouraged in adults with Beckers Muscular Dystrophy, anything appears better than nothing. Body composition, rather than body mass, should be monitored closely to identify any increase in body fat

Quality of life in adults with muscular dystrophy

Background Muscle weakness is a defining characteristic of Muscular Dystrophy (MD); however, yet while speculated, objective measures of muscle weakness has not been reported in relation to quality of life in adults with MD. Objectives 1) compare the self-reported QoL of adults with Duchenne MD (DMD), Beckers MD (BMD), Limb-Girdle MD (LGMD) and Fascioscapulohumeral MD (FSHD, and a non-MD (CTRL) group; 2) present and compare between groups measures of Impairment (Muscle Strength and Activities of Daily Living) and Perception (Fatigue, Pain and Self-Efficacy); and 3) identify associations between QoL domains and measures of Impairment and Perception (See above). Methods Seventy-Five males, including MD classifications DMD, BMD, LGMD, FSHD and CTRL, completed measures for QoL, Knee-Extension Maximal Voluntary Contraction (KEMVC), Fatigue, Pain, Self-Efficacy and Activities of Daily Living (ADL). Results QoL was lower across many domains in MD than CTRL. FSHD scored lower than DMD for mental wellbeing domains. KEMVC associated with Physical-Function domain for BMD. Pain, Self-Efficacy and ADLs associated with QoL domains, with Fatigue the most consistently associated. Conclusion The present study identified differences between MD classifications within self-perceptions of mental-health. Muscle weakness is a defining feature of MD; however, it doesn’t define QoL in adults with MD. A greater understanding of mental wellbeing, independence, and management of fatigue and pain, are required to improve QoL for adults with MD

The Association of Multiple Gene Variants with Ageing Skeletal Muscle Phenotypes in Elderly Women

There is a scarcity of studies that have investigated the role of multiple single nucleotide polymorphisms (SNPs) on a range of muscle phenotypes in an elderly population. The present study investigated the possible association of 24 SNPs with skeletal muscle phenotypes in 307 elderly Caucasian women (aged 60–91 years, 66.3 ± 11.3 kg). Skeletal muscle phenotypes included biceps brachii thickness, vastus lateralis cross-sectional areas, maximal hand grip strength, isometric knee extension and elbow flexion torque. Genotyping for 24 SNPs, chosen on their skeletal muscle structural or functional links, was conducted on DNA extracted from blood or saliva. Of the 24 SNPs, 10 were associated with at least one skeletal muscle phenotype. HIF1A rs11549465 was associated with three skeletal muscle phenotypes and PTK2 rs7460 and ACVR1B rs10783485 were each associated with two phenotypes. PTK2 rs7843014, COL1A1 rs1800012, CNTF rs1800169, NOS3 rs1799983, MSTN rs1805086, TRHR rs7832552 and FTO rs9939609 were each associated with one. Elderly women possessing favourable genotypes were 3.6–13.2% stronger and had 4.6–14.7% larger muscle than those with less favourable genotypes. These associations, together with future work involving a broader range of SNPs, may help identify individuals at particular risk of an age-associated loss of independence.</jats:p

Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status

Objective: Concussions are common match injuries in elite rugby, and reports exist of reduced cognitive function and long-term health consequences that can interrupt or end a playing career and produce continued ill health. The aim of this study was to investigate the association between elite rugby status and 8 concussion-associated risk polymorphisms. We hypothesized that concussion-associated risk genotypes and alleles would be underrepresented in elite rugby athletes compared with nonathletes. Design: A case-control genetic association study.Setting:  Institutional (university). Participants: Elite White male rugby athletes [n = 668, mean (SD) height 1.85 (0.07) m, mass 102 (12) kg, and age 29 (7) years] and 1015 nonathlete White men and women (48% men). Interventions: Genotype was the independent variable, obtained by PCR of genomic DNA using TaqMan probes.Main Outcome Measure:  Elite athlete status with groups compared using χ2 and odds ratio (OR). Results: The COMT rs4680 Met/Met (AA) genotype, Met allele possession, and Met allele frequency were lower in rugby athletes (24.8%, 74.6%, and 49.7%, respectively) than nonathletes (30.2%, 77.6%, and 54.0%; P &lt; 0.05). The Val/Val (GG) genotype was more common in elite rugby athletes than nonathletes (OR 1.39, 95% confidence interval 1.04-1.86). No other polymorphism was associated with elite athlete status. Conclusions: Elite rugby athlete status is associated with COMT rs4680 genotype that, acting pleiotropically, could affect stress resilience and behavioral traits during competition, concussion risk, and/or recovery from concussion. Consequently, assessing COMT rs4680 genotype might aid future individualized management of concussion risk among athletes.

Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes

Due to the high-velocity collision-based nature of elite rugby league and union, the risk of sustaining a concussion is high. Occurrence of and outcomes following a concussion are probably affected by the interaction of multiple genes in a polygenic manner. This study investigated whether suspected concussion-associated polygenic profiles of elite rugby athletes differed from non-athletes and between rugby union forwards and backs. We hypothesised that a total genotype score (TGS) using eight concussion-associated polymorphisms would be higher in elite rugby athletes than non-athletes, indicating selection for protection against incurring or suffering prolonged effects of, concussion in the relatively high-risk environment of competitive rugby. In addition, multifactor dimensionality reduction was used to identify genetic interactions. Contrary to our hypothesis, TGS did not differ between elite rugby athletes and non-athletes (p ≥ 0.065), nor between rugby union forwards and backs (p = 0.668). Accordingly, the TGS could not discriminate between elite rugby athletes and non-athletes (AUC ~0.5), suggesting that, for the eight polymorphisms investigated, elite rugby athletes do not have a more ‘preferable’ concussion-associated polygenic profile than non-athletes. However, the COMT (rs4680) and MAPT (rs10445337) GC allele combination was more common in rugby athletes (31.7%; p < 0.001) and rugby union athletes (31.8%; p < 0.001) than non-athletes (24.5%). Our results thus suggest a genetic interaction between COMT (rs4680) and MAPT (rs10445337) assists rugby athletes in achieving elite status. These findings need exploration vis-à-vis sport-related concussion injury data and could have implications for the management of inter-individual differences in concussion risk

Polymorphisms in PTK2 are associated with skeletal muscle specific force: an independent replication study

Purpose The aim of the study was to investigate two single nucleotide polymorphisms (SNP) in PTK2 for associations with human muscle strength phenotypes in healthy men. Methods Measurement of maximal isometric voluntary knee extension (MVCKE) torque, net MVCKE torque and vastus lateralis (VL) specific force, using established techniques, was completed on 120 Caucasian men (age = 20.6 ± 2.3 year; height = 1.79 ± 0.06 m; mass = 75.0 ± 10.0 kg; mean ± SD). All participants provided either a blood (n = 96) or buccal cell sample, from which DNA was isolated and genotyped for the PTK2 rs7843014 A/C and rs7460 A/T SNPs using real-time polymerase chain reaction. Results Genotype frequencies for both SNPs were in Hardy–Weinberg equilibrium (X 2 ≤ 1.661, P ≥ 0.436). VL specific force was 8.3% higher in rs7843014 AA homozygotes than C-allele carriers (P = 0.017) and 5.4% higher in rs7460 AA homozygotes than T-allele carriers (P = 0.029). No associations between either SNP and net MVCKE torque (P ≥ 0.094) or peak MVCKE torque (P ≥ 0.107) were observed. Conclusions These findings identify a genetic contribution to the inter-individual variability within muscle specific force and provides the first independent replication, in a larger Caucasian cohort, of an association between these PTK2 SNPs and muscle specific force, thus extending our understanding of the influence of genetic variation on the intrinsic strength of muscle.Published versio