The PPARGC1A Gly482Ser polymorphism is associated with elite long-distance running performance.

Success in long-distance running relies on multiple factors including oxygen utilisation and lactate metabolism, and genetic associations with athlete status suggest elite competitors are heritably predisposed to superior performance. The Gly allele of the PPARGC1A Gly482Ser rs8192678 polymorphism has been associated with endurance athlete status and favourable aerobic training adaptations. However, the association of this polymorphism with performance amongst long-distance runners remains unclear. Accordingly, this study investigated whether rs8192678 was associated with elite status and competitive performance of long-distance runners. Genomic DNA from 656 Caucasian participants including 288 long-distance runners (201 men, 87 women) and 368 non-athletes (285 men, 83 women) was analysed. Medians of the 10 best UK times (Top10) for 10 km, half-marathon and marathon races were calculated, with all included athletes having personal best (PB) performances within 20% of Top10 (this study's definition of "elite"). Genotype and allele frequencies were compared between athletes and non-athletes, and athlete PB compared between genotypes. There were no differences in genotype frequency between athletes and non-athletes, but athlete Ser allele carriers were 2.5% faster than Gly/Gly homozygotes (p = 0.030). This study demonstrates that performance differences between elite long-distance runners are associated with rs8192678 genotype, with the Ser allele appearing to enhance performance.

Collagen Gene Polymorphisms Previously Associated with Resistance to Soft-Tissue Injury Are More Common in Competitive Runners Than Nonathletes.

ABSTRACT: Dines, HR, Nixon, J, Lockey, SJ, Herbert, AJ, Kipps, C, Pedlar, CR, Day, SH, Heffernan, SM, Antrobus, MR, Brazier, J, Erskine, RM, Stebbings, GK, Hall, ECR, and Williams, AG. Collagen gene polymorphisms previously associated with resistance to soft-tissue injury are more common in competitive runners than nonathletes. J Strength Cond Res 37(4): 799-805, 2023-Single-nucleotide polymorphisms (SNPs) of collagen genes have been associated with soft-tissue injury and running performance. However, their combined contribution to running performance is unknown. We investigated the association of 2 collagen gene SNPs with athlete status and performance in 1,429 Caucasian subjects, including 597 competitive runners (354 men and 243 women) and 832 nonathletes (490 men and 342 women). Genotyping for COL1A1 rs1800012 (C > A) and COL5A1 rs12722 (C > T) SNPs was performed by a real-time polymerase chain reaction. The numbers of "injury-resistant" alleles from each SNP, based on previous literature (rs1800012 A allele and rs12722 C allele), were combined as an injury-resistance score (RScore, 0-4; higher scores indicate injury resistance). Genotype frequencies, individually and combined as an RScore, were compared between cohorts and investigated for associations with performance using official race times. Runners had 1.34 times greater odds of being rs12722 CC homozygotes than nonathletes (19.7% vs. 15.5%, p = 0.020) with no difference in the rs1800012 genotype distribution ( p = 0.659). Fewer runners had an RScore 0 of (18.5% vs. 24.7%) and more had an RScore of 4 (0.6% vs. 0.3%) than nonathletes ( p < 0.001). Competitive performance was not associated with the COL1A1 genotype ( p = 0.933), COL5A1 genotype ( p = 0.613), or RScore ( p = 0.477). Although not associated directly with running performance among competitive runners, a higher combined frequency of injury-resistant COL1A1 rs1800012 A and COL5A1 rs12722 C alleles in competitive runners than nonathletes suggests these SNPs may be advantageous through a mechanism that supports, but does not directly enhance, running performance.

Gene variants previously associated with reduced soft tissue injury risk: Part 1 - independent associations with elite status in rugby.

There is growing evidence of genetic contributions to tendon and ligament pathologies. Given the high incidence and severity of tendon and ligament injuries in elite rugby, we studied whether 13 gene polymorphisms previously associated with tendon/ligament injury were associated with elite athlete status. Participants from the RugbyGene project were 663 elite Caucasian male rugby athletes (RA) (mean (standard deviation) height 1.85 (0.07) m, mass 101 (12) kg, age 29 (7) yr), including 558 rugby union athletes (RU) and 105 rugby league athletes. Non-athletes (NA) were 909 Caucasian men and women (56% female; height 1.70 (0.10) m, mass 72 (13) kg, age 41 (23) yr). Genotypes were determined using TaqMan probes and groups compared using Χ2 and odds ratio (OR). COLGALT1 rs8090 AA genotype was more frequent in RA (27%) than NA (23%; P = 0.006). COL3A1 rs1800255 A allele was more frequent in RA (26%) than NA (23%) due to a greater frequency of GA genotype (39% vs 33%). For MIR608 rs4919510, RA had 1.7 times the odds of carrying the CC genotype compared to NA. MMP3 rs591058 TT genotype was less common in RA (25.1%) than NA (31.2%; P < 0.04). For NID1 rs4660148, RA had 1.6 times the odds of carrying the TT genotype compared to NA. It appears that elite rugby athletes have an inherited advantage that contributes to their elite status, possibly via resistance to soft tissue injury. These data may, in future, assist personalised management of injury risk amongst athletes.Highlights The elite rugby athletes we studied had differing genetic characteristics to non-athletes regarding genetic variants previously associated with soft-tissue injury risk.COLGALT1 rs8090, COL3A1 rs1800255, MIR608 rs4919510, MMP3 rs591058 and NID1 rs4660148 were all associated with elite status in rugby.We propose that elite rugby athletes might possess an inherited resistance to soft tissue injury, which has enabled them to achieve elite status despite exposure to the high-risk environment of elite rugby.

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 χ 2 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 < 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.

Gene variants previously associated with reduced soft-tissue injury risk: Part 2 - Polygenic associations with elite status in Rugby.

Part 1 of this genetic association series highlighted several genetic variants independently associated with elite status in rugby. However, it is highly likely that the genetic influence on elite status is polygenic due to the interaction of multiple genes. Therefore, the aim of the present study was to investigate whether polygenic profiles of elite rugby athletes differed from non-athletes utilising 13 genetic polymorphisms previously associated with tendon/ligament injury. Total genotype score (TGS) was calculated and multifactor dimensionality reduction (MDR) was used to calculate SNP-SNP epistasis interactions. Based on our elite rugby data from Part 1, mean TGS was significantly higher in elite rugby athletes (52.1 ± 10.7) than non-athletes (48.7 ± 10.8). There were more elite rugby athletes (54%) within the upper TGS quartile, and fewer (46%) within the lower quartile, compared to non-athletes (31% and 69%, respectively; P = 5·10-5), and the TGS was able to distinguish between elite rugby athletes and non-athletes (area under the curve = 0.59; 95% confidence interval 0.55-0.63; P = 9·10-7). Furthermore, MDR identified a three-SNP model of COL5A1 rs12722, COL5A1 rs3196378 and MIR608 rs4919510 that was best able to predict elite athlete status, with a greater frequency of the CC-CC-CC genotype combination in elite rugby athletes (9.8%) than non-athletes (5.3%). We propose that elite rugby athletes possess "preferable" musculoskeletal soft-tissue injury-associated polygenic profiles that have helped them achieve success in the high injury risk environment of rugby. These data may, in future, have implications for the individual management of musculoskeletal soft-tissue injury.HighlightsElite rugby athletes have preferable polygenic profiles to non-athletes in terms of genetic variants previously associated with musculoskeletal soft-tissue injury.The total genotype score was able to distinguish between elite rugby athletes and non-athletes.COL5A1 rs12722, COL5A1 rs3196378 and MIR608 rs4919510 produced the best model for predicting elite athlete status.We propose that elite rugby athletes may have an inherited advantage to achieving elite status due to an increased resistance to soft-tissue injury.

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.

Genetic Polymorphisms Related to VO2max Adaptation Are Associated With Elite Rugby Union Status and Competitive Marathon Performance.

PURPOSE: Genetic polymorphisms have been associated with the adaptation to training in maximal oxygen uptake (V˙O2max). However, the genotype distribution of selected polymorphisms in athletic cohorts is unknown, with their influence on performance characteristics also undetermined. This study investigated whether the genotype distributions of 3 polymorphisms previously associated with V˙O2max training adaptation are associated with elite athlete status and performance characteristics in runners and rugby athletes, competitors for whom aerobic metabolism is important. METHODS: Genomic DNA was collected from 732 men including 165 long-distance runners, 212 elite rugby union athletes, and 355 nonathletes. Genotype and allele frequencies of PRDM1 rs10499043 C/T, GRIN3A rs1535628 G/A, and KCNH8 rs4973706 T/C were compared between athletes and nonathletes. Personal-best marathon times in runners, as well as in-game performance variables and playing position, of rugby athletes were analyzed according to genotype. RESULTS: Runners with PRDM1 T alleles recorded marathon times ∼3 minutes faster than CC homozygotes (02:27:55 [00:07:32] h vs 02:31:03 [00:08:24] h, P = .023). Rugby athletes had 1.57 times greater odds of possessing the KCNH8 TT genotype than nonathletes (65.5% vs 54.7%, χ2 = 6.494, P = .013). No other associations were identified. CONCLUSIONS: This study is the first to demonstrate that polymorphisms previously associated with V˙O2max training adaptations in nonathletes are also associated with marathon performance (PRDM1) and elite rugby union status (KCNH8). The genotypes and alleles previously associated with superior endurance-training adaptation appear to be advantageous in long-distance running and achieving elite status in rugby union.

Genetic Factors That Could Affect Concussion Risk in Elite Rugby.

Elite rugby league and union have some of the highest reported rates of concussion (mild traumatic brain injury) in professional sport due in part to their full-contact high-velocity collision-based nature. Currently, concussions are the most commonly reported match injury during the tackle for both the ball carrier and the tackler (8-28 concussions per 1000 player match hours) and reports exist of reduced cognitive function and long-term health consequences that can end a playing career and produce continued ill health. Concussion is a complex phenotype, influenced by environmental factors and an individual's genetic predisposition. This article reviews concussion incidence within elite rugby and addresses the biomechanics and pathophysiology of concussion and how genetic predisposition may influence incidence, severity and outcome. Associations have been reported between a variety of genetic variants and traumatic brain injury. However, little effort has been devoted to the study of genetic associations with concussion within elite rugby players. Due to a growing understanding of the molecular characteristics underpinning the pathophysiology of concussion, investigating genetic variation within elite rugby is a viable and worthy proposition. Therefore, we propose from this review that several genetic variants within or near candidate genes of interest, namely APOE, MAPT, IL6R, COMT, SLC6A4, 5-HTTLPR, DRD2, DRD4, ANKK1, BDNF and GRIN2A, warrant further study within elite rugby and other sports involving high-velocity collisions.

Anthropometric and Physiological Characteristics of Elite Male Rugby Athletes.

Brazier, J, Antrobus, M, Stebbings, GK, Day, SH, Callus, P, Erskine, RM, Bennett, MA, Kilduff, LP, and Williams, AG. Anthropometric and physiological characteristics of elite male rugby athletes. J Strength Cond Res 34(6): 1790-1801, 2020-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 body 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 seconds, backs ∼1.77 seconds; 10 m: RL forwards ∼1.9 seconds, backs ∼1.83 seconds). 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.

Tendon and Ligament Injuries in Elite Rugby: The Potential Genetic Influence.

This article reviews tendon and ligament injury incidence and severity within elite rugby union and rugby league. Furthermore, it discusses the biological makeup of tendons and ligaments and how genetic variation may influence this and predisposition to injury. Elite rugby has one of the highest reported injury incidences of any professional sport. This is likely due to a combination of well-established injury surveillance systems and the characteristics of the game, whereby high-impact body contact frequently occurs, in addition to the high intensity, multispeed and multidirectional nature of play. Some of the most severe of all these injuries are tendon and ligament/joint (non-bone), and therefore, potentially the most debilitating to a player and playing squad across a season or World Cup competition. The aetiology of these injuries is highly multi-factorial, with a growing body of evidence suggesting that some of the inter-individual variability in injury susceptibility may be due to genetic variation. However, little effort has been devoted to the study of genetic injury traits within rugby athletes. Due to a growing understanding of the molecular characteristics underpinning the aetiology of injury, investigating genetic variation within elite rugby is a viable and worthy proposition. Therefore, we propose several single nucleotide polymorphisms within candidate genes of interest; COL1A1, COL3A1, COL5A1, MIR608, MMP3, TIMP2, VEGFA, NID1 and COLGALT1 warrant further study within elite rugby and other invasion sports.

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes.

Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50-85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case-control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene-environment interactions-in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically "extreme" population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully.

No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes.

BACKGROUND: Studies investigating associations between ACTN3 R577X and ACE I/D genotypes and endurance athletic status have been limited by small sample sizes from mixed sport disciplines and lack quantitative measures of performance. AIM: To examine the association between ACTN3 R577X and ACE I/D genotypes and best personal running times in a large homogeneous cohort of endurance runners. METHODS: We collected a total of 1064 personal best 1500, 3000, 5000 m and marathon running times of 698 male and female Caucasian endurance athletes from six countries (Australia, Greece, Italy, Poland, Russia and UK). Athletes were genotyped for ACTN3 R577X and ACE ID variants. RESULTS: There was no association between ACTN3 R577X or ACE I/D genotype and running performance at any distance in men or women. Mean (SD) marathon times (in s) were for men: ACTN3 RR 9149 (593), RX 9221 (582), XX 9129 (582) p = 0.94; ACE DD 9182 (665), ID 9214 (549), II 9155 (492) p = 0.85; for women: ACTN3 RR 10796 (818), RX 10667 (695), XX 10675 (553) p = 0.36; ACE DD 10604 (561), ID 10766 (740), II 10771 (708) p = 0.21. Furthermore, there were no associations between these variants and running time for any distance in a sub-analysis of athletes with personal records within 20% of world records. CONCLUSIONS: Thus, consistent with most case-control studies, this multi-cohort quantitative analysis demonstrates it is unlikely that ACTN3 XX genotype provides an advantage in competitive endurance running performance. For ACE II genotype, some prior studies show an association but others do not. Our data indicate it is also unlikely that ACE II genotype provides an advantage in endurance running.

COL5A1 gene variants previously associated with reduced soft tissue injury risk are associated with elite athlete status in rugby.

BACKGROUND: Two common single nucleotide polymorphisms within the COL5A1 gene (SNPs; rs12722 C/T and rs3196378 C/A) have previously been associated with tendon and ligament pathologies. Given the high incidence of tendon and ligament injuries in elite rugby athletes, we hypothesised that both SNPs would be associated with career success. RESULTS: In 1105 participants (RugbyGene project), comprising 460 elite rugby union (RU), 88 elite rugby league athletes and 565 non-athlete controls, DNA was collected and genotyped for the COL5A1 rs12722 and rs3196378 variants using real-time PCR. For rs12722, the injury-protective CC genotype and C allele were more common in all athletes (21% and 47%, respectively) and RU athletes (22% and 48%) than in controls (16% and 41%, P ≤ 0.01). For rs3196378, the CC genotype and C allele were overrepresented in all athletes (23% and 48%) and RU athletes (24% and 49%) compared with controls (16% and 41%, P ≤ 0.02). The CC genotype in particular was overrepresented in the back and centres (24%) compared with controls, with more than twice the odds (OR = 2.25, P = 0.006) of possessing the injury-protective CC genotype. Furthermore, when considering both SNPs simultaneously, the CC-CC SNP-SNP combination and C-C inferred allele combination were higher in all the athlete groups (≥18% and ≥43%) compared with controls (13% and 40%; P = 0.01). However, no genotype differences were identified for either SNP when RU playing positions were compared directly with each other. CONCLUSION: It appears that the C alleles, CC genotypes and resulting combinations of both rs12722 and rs3196378 are beneficial for rugby athletes to achieve elite status and carriage of these variants may impart an inherited resistance against soft tissue injury, despite exposure to the high-risk environment of elite rugby. These data have implications for the management of inter-individual differences in injury risk amongst elite athletes.

Genetic Testing for Sports Performance, Responses to Training and Injury Risk: Practical and Ethical Considerations.

This paper addresses practical and ethical considerations regarding genetic tests to predict performance and/or risk of exercise-related injury or illness. Various people might wish to conduct sport-related genetic tests for a variety of reasons. For example, an individual might seek personal genetic information to help guide their own sport participation. A sports coach might wish to test young athletes to aid team selection or individualize training. A physician might want to predict the risk of injury or illness in athletes and advise regarding selection or preventative measures. An insurance company might seek to estimate the risk of career-threatening injury for athletes based partly on genetic information. Whilst this information is, in part, encoded in our DNA sequence, the available tests allow generally only a poor prediction of the aforementioned variables. In other words, the current genetic tests and analysis methods are not powerful enough to inform important decisions in sport to a substantial degree. It is particularly disappointing that more than half of the commercially available genetic tests related to exercise and sport do not appear to identify publicly the genetic variants they assess, making scrutiny by academic scholars and consumers (or their representatives) impossible. There are also challenging ethical issues to consider. For example, the imposition of genetic tests on individuals (especially young people) by third parties is potentially susceptible to abuse. Scientists and practitioners should understand the limitations of the tests currently available, the ethical concerns and the importance of counselling before and after testing so that they are only used in a responsible manner.

Genomics in rugby union: A review and future prospects.

This article introduces some aspects of sports genomics in a rugby union context, considers the rugby-specific genetic data in the published literature and outlines the next research steps required if the potential applications of genetic technology in rugby union, also identified here, are to become possible. A substantial proportion of the inter-individual variation for many traits related to rugby performance, including strength, short-term muscle power, VO2 max, injury susceptibility and the likelihood of being an elite athlete is inherited and can be investigated using molecular genetic techniques. In sports genomics, significant efforts have been made in recent years to develop large DNA biobanks of elite athletes for detailed exploration of the heritable bases of those traits. However, little effort has been devoted to the study of rugby athletes, and most of the little research that has focused on rugby was conducted with small cohorts of non-elite players. With steadily growing knowledge of the molecular mechanisms underpinning complex performance traits and the aetiology of injury, investigating sports genomics in the context of rugby is now a viable proposition and a worthwhile endeavour. The RugbyGene project we describe briefly in this article is a multi-institutional research collaboration in rugby union that will perform molecular genetic analyses of varying complexity. Genetic tests could become useful tools for rugby practitioners in the future and provide complementary and additional information to that provided by the non-genetic tests currently used.

The human patellar tendon moment arm assessed in vivo using dual-energy X-ray absorptiometry.

Accurate assessment of muscle-tendon forces in vivo requires knowledge of the muscle-tendon moment arm. Dual-energy X-ray absorptiometry (DXA) can produce 2D images suitable for visualising both tendon and bone, thereby potentially allowing the moment arm to be measured but there is currently no validated DXA method for this purpose. The aims of this study were (i) to compare in vivo measurements of the patellar tendon moment arm (dPT) assessed from 2D DXA and magnetic resonance (MR) images and (ii) to compare the reliability of the two methods. Twelve healthy adults (mean ± SD: 31.4 ± 9.5 yr; 174.0 ± 9.5 cm; 76.2 ± 16.6 kg) underwent two DXA and two MR scans of the fully extended knee at rest. The tibiofemoral contact point (TFCP) was used as the centre of joint rotation in both techniques, and the dPT was defined as the perpendicular distance from the patellar tendon axis to the TFCP. The dPT was consistently longer when assessed via DXA compared to MRI (+3.79 ± 1.25 mm or +9.78 ± 3.31%; P<0.001). The test-retest reliability of the DXA [CV=2.13%; ICC=0.94; ratio limits of agreement (RLA)=1.01 (*/÷1.07)] and MR [(CV=2.27%; ICC=0.96; RLA=1.00 (*/÷1.07)] methods was very high and comparable between techniques. Moreover, the RLA between the mean DXA and MRI dPT values [1.097 (*/÷1.061)] demonstrated very strong agreement between the two methods. In conclusion, highly reproducible dPT measurements can be determined from DXA imaging with the knee fully extended at rest. This has implications for the calculation of patellar tendon forces in vivo where MR equipment is not available.

Variability and distribution of muscle strength and its determinants in humans.

INTRODUCTION: Inter-individual variability in measurements of muscle strength and its determinants was identified to: (1) produce a normative data set describing the normal range and (2) determine whether some measurements are more informative than others when evaluating inter-individual differences. METHODS: Functional and morphological characteristics of the vastus lateralis were measured in 73 healthy, untrained adult men. RESULTS: Inter-individual variability (coefficient of variation) was greater for isometric maximal voluntary contraction (MVC) torque (18.9%) compared with fascicle force (14.6%; P=0.025) and physiological cross-sectional area (PCSA; 17.2%) compared with anatomical cross-sectional area (ACSA, 13.0%; P<0.0005). The relationship between ACSA and isometric MVC torque (r(2) =0.56) was weaker than that between PCSA and fascicle force (r(2) =0.68). CONCLUSIONS: These results provide a normative data set on inter-individual variability in a variety of muscle strength-related measurements and illustrate the benefit of using more stringent measures of muscle properties. Muscle Nerve 49: 879-886, 2014.

The HIF1A gene Pro582Ser polymorphism in Russian strength athletes.

Hypoxia-inducible factor-1α (encoded by HIF1A gene) controls a number of genes that are implicated in various cellular functions including glycolysis and cell proliferation and differentiation. The rs11549465 C > T polymorphism in the HIF1A gene, which produces the amino acid substitution Pro582Ser, increases protein stability and transcriptional activity and, therefore, improves glucose metabolism. The aim of our study was to investigate the association between the HIF1A Pro582Ser polymorphism and elite strength athlete status. A total of 208 Russian strength athletes (122 weightlifters and 86 wrestlers) of regional or national competitive standard and 1,413 controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. We found that the frequency of the HIF1A 582Ser variant was significantly higher in weightlifters (13.1%, p = 0.0031) and wrestlers (15.7%, p = 0.0002) compared with the controls (7.5%). Additionally, the highest (21.1%, p = 0.0052) frequency of the 582Ser variant was found in a group of elite strength athletes. Thus, our study provides evidence for an association between the HIF1A gene Pro582Ser polymorphism and elite strength athlete status. Although more replication studies are needed, the preliminary data suggest an opportunity to use the analysis of HIF1A polymorphism along with other gene variations and standard phenotypic assessment in sports selection.

Variation in the uncoupling protein 2 and 3 genes and human performance.

Uncoupling proteins 2 and 3 (UCP2 and UCP3) may negatively regulate mitochondrial ATP synthesis and, through this, influence human physical performance. However, human data relating to both these issues remain sparse. Examining the association of common variants in the UCP3/2 locus with performance phenotypes offers one means of investigation. The efficiency of skeletal muscle contraction, delta efficiency (DE), was assessed by cycle ergometry in 85 young, healthy, sedentary adults both before and after a period of endurance training. Of these, 58 were successfully genotyped for the UCP3-55C>T (rs1800849) and 61 for the UCP2-866G>A (rs659366) variant. At baseline, UCP genotype was unrelated to any physical characteristic, including DE. However, the UCP2-866G>A variant was independently and strongly associated with the DE response to physical training, with UCP2-866A allele carriers exhibiting a greater increase in DE with training (absolute change in DE of -0.2 ± 3.6% vs. 1.7 ± 2.8% vs. 2.3 ± 3.7% for GG vs. GA vs. AA, respectively; P = 0.02 for A allele carriers vs. GG homozygotes). In multivariate analysis, there was a significant interaction between UCP2-866G>A and UCP3-55C>T genotypes in determining changes in DE (adjusted R(2) = 0.137; P value for interaction = 0.003), which was independent of the effect of either single polymorphism or baseline characteristics. In conclusion, common genetic variation at the UCP3/2 gene locus is associated with training-related improvements in DE, an index of skeletal muscle performance. Such effects may be mediated through differences in the coupling of mitochondrial energy transduction in human skeletal muscle, but further mechanistic studies are required to delineate this potential role.

Genetics of muscle strength and power: polygenic profile similarity limits skeletal muscle performance.

Environmental and genetic factors influence muscle function, resulting in large variations in phenotype between individuals. Multiple genetic variants (polygenic in nature) are thought to influence exercise-related phenotypes, yet how the relevant polymorphisms combine to influence muscular strength in individuals and populations is unclear. In this analysis, 22 genetic polymorphisms were identified in the literature that have been associated with muscular strength and power phenotypes. Using typical genotype frequencies, the probability of any given individual possessing an "optimal" polygenic profile was calculated as 0.0003% for the world population. Future identification of additional polymorphisms associated with muscular strength phenotypes would most likely reduce that probability even further. To examine the genetic potential for muscular strength within a human population, a "total genotype score" was generated for each individual within a hypothetical population of one million. The population expressed high similarity in polygenic profile with no individual differing by more than seven genotypes from a typical profile. Therefore, skeletal muscle strength potential within humans appears to be limited by polygenic profile similarity. Future research should aim to replicate more genotype-phenotype associations for muscular strength, because only five common genetic polymorphisms identified to date have positive replicated findings.