ACTN3 R577X Research Articles

ACTN3 R577X Polymorphism Is Associated With the Incidence and Severity of Injuries in Professional Football Players.

The ACTN3 R577X gene variant results in the absence of the α-actinin-3 protein in ∼18% of humans worldwide and has been associated with athletic performance and increased susceptibility to eccentric muscle damage. The aim of this study was to investigate the association between ACTN3 R577X variant and indirect muscle disorders/injuries in professional football players. A case-control, genotype-phenotype association study. Two hundred fifty-seven male professional Italian football players (from Serie A, Primavera, Allievi, and Giovanissimi; age = 21.2 ± 5.3 years) and 265 nonathletic controls were recruited for the study. Genomic DNA was extracted using a buccal swab, and the ACTN3 R577X genotype was performed using a PCR method. Structural-mechanical injuries and functional muscle disorders were collected from a subgroup of 169 football players during the period of 2009 to 2014. We hypothesized that the 577XX genotype would be associated with higher predisposition to muscle injuries (compared with the other genotypes). ACTN3 XX (α-actinin-3 deficiency) players had 2.66 higher odds for an injury incidence than their ACTN3 RR counterparts (95% confidence interval [CI]: 1.09-6.63, P = 0.02), whereas RX and RR players had similar injury incidence. Furthermore, ACTN3 XX players had 2.13 higher odds for having a severe injury compared with their RR counterparts (95% CI: 1.25-3.74, P = 0.0054), whereas RX individuals had 1.63 higher odds for having a severe injury compared with the RR players (95% CI: 1.10-2.40, P = 0.015). The ACTN3 R577X polymorphism is associated with the incidence and severity of muscle injuries in professional football players; players with the ACTN3 577XX genotype have higher odds of having muscle injuries than their RR counterparts. Discovering the complex relationship between gene variants and muscle injuries may assist coaches, physiologists, and the medical community to development tailored injury prevention program for football players, which could provide a new edge for successful competition.

ACTN3 R577X Genotype Is Associated with ACTN3 Protein Expression Levels and Myosin Heavy Chain Composition in Japanese College-Level Male Sprinters

ACTN3 R577X Genotype Is Associated with ACTN3 Protein Expression Levels and Myosin Heavy Chain Composition in Japanese College-Level Male Sprinters

Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease.

A common null polymorphism in the ACTN3 gene (rs1815739:C>T) results in replacement of an arginine (R) with a premature stop codon (X) at amino acid 577 in the fast muscle protein α-actinin-3. The ACTN3 p.Arg577Ter allele (aka p.R577* or R577X) has undergone positive selection, with an increase in the X allele frequency as modern humans migrated out of Africa into the colder, less species-rich Eurasian climates suggesting that the absence of α-actinin-3 may be beneficial in these conditions. Approximately 1.5 billion people worldwide are completely deficient in α-actinin-3. While the absence of α-actinin-3 influences skeletal muscle function and metabolism this does not result in overt muscle disease. α-Actinin-3 deficiency (ACTN3 XX genotype) is constantly underrepresented in sprint/power performance athletes. However, recent findings from our group and others suggest that the ACTN3 R577X genotype plays a role beyond athletic performance with effects observed in ageing, bone health, and inherited muscle disorders such as McArdle disease and Duchenne muscle dystrophy. In this review, we provide an update on the current knowledge regarding the influence of ACTN3 R577X on skeletal muscle function and its potential biological and clinical implications. We also outline future research directions to explore the role of α-actinin-3 in healthy and diseased populations.

Evidence for a Role of ACTN3 R577X Polymorphism in Football Player's Career Progression.

The aim was to investigate a possible role of the ACTN3 R577X polymorphism in a Brazilian football player's career progression. 2 questions were formulated: 1. Does ACTN3 polymorphism affect the probability of an individual being a professional football player? 2. Does this polymorphism affect the progression of the athlete throughout his career? The study included 353 players from first division Brazilian football clubs in the following categories: under-14 (U-14), U-15, U-17, U-20, and professional (PRO). The control group (CON) was composed of 100 healthy non-athletes. The chi-squared test was used to assess differences between the allele and genotype frequencies. Comparing football categories, the XX genotype was less frequent among professional players than in the U-20 (p<0.05) or the U-15 category (p<0.05). The RX genotype also presented more frequently in the PRO category than the U-14 category (p<0.05). Moreover, a trend towards a higher frequency of the RX genotype and a lower frequency of the XX genotype was observed in the professional category compared to U-20. These results suggest that the genotype in the ACTN3 polymorphism affects the probability of a football player progressing throughout his career and becoming professional, meaning that playing football selects against the ACTN3 XX genotype.

The stiffness response of type IIa fibres after eccentric exercise-induced muscle damage is dependent on ACTN3 r577X polymorphism

The aim of the study was to determine the effect of α-actinin-3 (ACTN3) deficiency (XX) on muscle damage induced by an eccentric exercise bout. In this purpose, 4 RR and 4 XX individuals performed an intensive eccentric knee flexion exercise on an isokinetic dynamometer. Muscle biopsies, blood and pain scores were taken before and after the exercise to determine the extent of the exercise-induced damage and the effect of the ACTN3 R577X polymorphism. Maximal isometric strength of the quadriceps and single fibre properties were compared before and after the exercise. The drop in maximal isometric strength of the quadriceps at 45° knee flexion following the eccentric exercise bout was on average 37% 24 h post-exercise. The decrease in force was also apparent in isolated type IIa fibres (8%; P = 0.02), but not in type I fibres (P = 0.88). Creatine kinase and myoglobin plasma levels increased in all participants at least by 55% and 87%, respectively (P < 0.05). In addition, mRNA levels of markers for muscle regeneration and muscle remodelling increased after the eccentric exercise (P < 0.05), however, independently from ACTN3 R577X genotype. The mRNA level of nuclear factor of activated T-cells 1 (NFATc1) decreased after the eccentric exercise only in XX genotypes (P < 0.05). The stiffness of type IIa, but not type I muscle fibres increased only in RR individuals after the eccentric exercise (P < 0.05). While no major effect of α-actinin-3 deficiency on susceptibility to muscle damage was found acutely, the increased stiffness response in fast RR fibres might be a protection mechanism from muscle damage during a subsequent eccentric exercise bout.

More than a 'speed gene': ACTN3 R577X genotype, trainability, muscle damage, and the risk for injuries.

A common null polymorphism (rs1815739; R577X) in the gene that codes for α-actinin-3 (ACTN3) has been related to different aspects of exercise performance. Individuals who are homozygous for the X allele are unable to express the α-actinin-3 protein in the muscle as opposed to those with the RX or RR genotype. α-actinin-3 deficiency in the muscle does not result in any disease. However, the different ACTN3 genotypes can modify the functioning of skeletal muscle during exercise through structural, metabolic or signaling changes, as shown in both humans and in the mouse model. Specifically, the ACTN3 RR genotype might favor the ability to generate powerful and forceful muscle contractions. Leading to an overall advantage of the RR genotype for enhanced performance in some speed and power-oriented sports. In addition, RR genotype might also favor the ability to withstand exercise-induced muscle damage, while the beneficial influence of the XX genotype on aerobic exercise performance needs to be validated in human studies. More information is required to unveil the association of ACTN3 genotype with trainability and injury risk during acute or chronic exercise.

The relationship between ACTN3 R577X gene polymorphism and physical performance in amateur soccer players and sedentary individuals.

The aim of this study was to determine the distribution of ACTN3 R577X gene polymorphism in soccer players and sedentary individuals, and to investigate the relationship of this distribution with performance tests. A total of 100 soccer players and 101 sedentary individuals were enrolled in the study. Standing long jump and countermovement jump (with arm swing, without arm swing and repeated) scores were recorded, using a jump meter. Maximum VO2 levels were measured using a treadmill-connected cardiopulmonary exercise device, Masterscreen CPX. ACTN3 R577X polymorphism was evaluated by real-time PCR. ACTN3 R577X genotype distribution was found to be similar in soccer players and controls (p>0.05). The only statistically significant finding was a shorter countermovement jump with arm swing scores in the RR-genotyped soccer players, compared with their RX genotyped counterparts (p<0.05). In the soccer player group, RX-genotyped subjects were observed to have lower respiratory threshold values compared with RR-genotyped subjects (p<0.05). No significant correlation was detected between this distribution and performance test results. ACTN3 R577X genotype distribution was found to have no effect on sprint and endurance characteristics in amateur soccer players. The ACTN3 R577X polymorphism may not be a specific enough genetic marker to determine athletic performance in soccer.

PO-008 Influences of ACE I/D and ACTN3 R577X polymorphisms in elite female soccer athletes

Objective The performance phenotype is regulated by polygenes .There were few reports about the cumulative effect of the I/D polymorphism in the angiotensin I-converting enzyme (ACE) gene and ACTN3 in athletes.This study was to investigate the association of ACEI/D and ACTN3 R577X polymorphisms with the performance of Chinese elite female soccer athletes for the first time. &#x0D; Methods The genotype distributions of ACE I/D and ACTN3 R577X in the athlete group (N=92) and the control group of Chinese females (N=200) were evaluated via PCR and compared.&#x0D; Results Regarding the distribution of ACE polymorphisms, the genotype frequency was indifferent between the athletes (II 40.2%, ID 46.7%, DD 13.1%) and the controls (II 42%, ID 48%, DD 10%) based on the chi-square test. No difference in the I/D allele frequency was observed between the athlete group (I allele: 59.25%; D allele: 40.75%) and the control group (I allele: 60.8%; D allele: 39.2%). Regarding the distribution of ACTN3 polymorphisms, the genotype frequency was significantly different between the athletes (XX 0%, XR 53.3%, RR 46.7%) and the controls (XX 16%, XR 44%, RR 40%). The allele frequency was observed no different between the athlete and the control group (X allele:34.8%/41.7%; R allele: 65.2%/58.3%, respectively). The ACE and ACTN3 genotype combinations (II/ID/DD+RR/XR) significantly differed between the athletes and the controls by χ2 test (p&lt;0.05).&#x0D; Conclusions These results suggested that the Chinese elite female soccer athletes were more likely to harbor the I allele and the R allele and that the combination of ACE II/ID and ACTN3 RR/XR was a synergetic determinant of the athletic performance of females in soccer.

Association of glutathione S-transferase M1 and T1 null/present polymorphism with physical performance in the Korean population.

Human physical performance is a highly complex phenotype that is influenced by various factors. In particular, genetic factors related to muscle fiber type, bone density, muscle performance, and metabolic processes are known to contribute in varying degrees to athlete status and physical performance in various ethnic groups. To investigate the relationship between these genetic factors and physical performances, we genotyped five genetic polymorphisms (ACE Ins/Del, ACTN3 R577X, ER-α C/T, GSTM1 null/present, and GSTT1 null/present) in 111 Korean athletes and 145 controls. We examined genotype and allele frequency differences between athletes and control groups, along with the odds ratios, using Chi square. One-way analysis of variance (ANOVA) was used to test the significance of differences in continuous variables between the multiple genetic polymorphisms and physical performance test results. The GSTM1 polymorphism exhibited a highly significant association in athletes (p = 0.017). Combined analysis of GSTM1 and GSTT1 also revealed significant differences between athletes and controls (p < 0.05). In the analysis of physical performance within athletes, the ER-α gene polymorphism was associated with the sargent jump and the side-step (p < 0.05), and the GSTM1 gene polymorphism was significantly associated with the 20m shuttle run and sit-up (p < 0.05). Thus, our data imply that GSTM1 and ER-α gene polymorphisms were associated with physical performance in Korean athletes, although functional studies with larger sample sizes are necessary to elaborate upon these findings.

Readthrough of ACTN3 577X nonsense mutation produces full-length α-actinin-3 protein

The ACTN3 gene encodes α-actinin-3 protein, which stabilizes the contractile apparatus at the Z-line in skeletal muscle cell fast fibers. A nonsense mutation of the arginine (R) at the codon for amino acid 577 of the ACTN3 gene generates a premature termination codon (PTC) and produces the R577X polymorphism in humans (X specifies translational termination). The ACTN3 577X genotype abolishes α-actinin-3 protein production due to targeted degradation of the mutant transcript by the cellular nonsense-mediated mRNA decay (NMD) system, which requires mRNA splicing. In humans, α-actinin-3 deficiency can decrease sprinting and power performance as well as skeletal muscle mass and strength. Here we investigated whether suppression of the in-frame PTC induced by treatment with the aminoglycosides gentamicin and G418 that promote termination codon readthrough could allow production of full-length α-actinin-3 protein from ACTN3 577X. We constructed expression plasmids encoding mature mRNA that lacks introns or pre-mRNA, which carries introns for the ACTN3 577X gene (X and Xpre, respectively) and transfected the constructs into HEK293 cells. Similar constructs for the ACTN3 577R gene were used as controls. HEK293 cells carrying the X gene, but not the Xpre gene, expressed exogenous truncated α-actinin-3 protein, indicating NMD-mediated suppression of exogenous Xpre expression. Cells treated with aminoglycosides produced exogenous full-length α-actinin-3 protein in X-transfected cells, but not in Xpre-transfected cells. The NMD inhibitor caffeine prevented suppression of Xpre expression and thereby induced production of full-length α-actinin-3 protein in the presence of aminoglycoside. Together these results indicate that the ACTN3 R577X polymorphism could be a novel target for readthrough therapy, which may affect athletic and muscle performance in humans.

ACE I/D and ACTN3 R577X genotypes, muscular and cardiovascular fitness in Malay males

ACE I/D and ACTN3 R577X genotypes, muscular and cardiovascular fitness in Malay males

Analysis of sports-relevant polymorphisms in a large Brazilian cohort of top-level athletes.

In recent years, there have been an increasing number of genetic variants associated with athletic phenotypes. Here, we selected a set of sports-relevant polymorphisms that have been previously suggested as genetic markers for human physical performance, and we examined their association with athletic status in a large cohort of Brazilians. We evaluated a sample of 1,622 individuals, in which 966 were nonathletes, and 656 were athletes: 328 endurance athletes and 328 power athletes. Only the AGT M268T minor allele was nominally associated with the endurance status. Conversely, we found that seven polymorphisms are more frequent in power athletes (MCT1 D490E, AGT M268T, PPARG P12A, PGC1A G482S, VEGFR2 Q472H, NOS3 C/T, and ACTN3 R577X). For all of these polymorphisms, power athletes were more likely than nonathletes or endurance athletes to carry the major allele or the homozygous genotype for the major allele. In particular, MCT1 D490E, AGT M268T, NOS3 C/T, and ACTN3 R577X showed stronger associations. Our findings support a role for these variants in the achievement of power athletic status in Brazilians: MCT1 D490E (T allele), AGT M268T (G allele), PPARG (C allele), PGC1A G482S (C allele), VEGFR2 Q472H (T allele), NOS3 C/T (T allele), and ACTN3 R577X (R allele).

ACTN3 genotype and physical function and frailty in an elderly Chinese population: the Rugao Longevity and Ageing Study.

To examine the associations of the actinin alpha 3 gene (ACTN3) R577X polymorphism with physical performance and frailty in an older Chinese population. Data from 1,463 individuals (57.8% female) aged 70-87 years from the Rugao Longevity and Ageing Study were used. The associations between R577X and timed 5-m walk, grip strength, timed Up and Go test, and frailty index (FI) based on deficits of 23 laboratory tests (FI-Lab) were examined. Analysis of variance and linear regression models were used to evaluate the genetic effects of ACTN3 R577X on physical performance and FI-Lab. The XX and RX genotypes of the ACTN3 R557X polymorphism accounted for 17.1 and 46.9%, respectively. Multivariate regression analysis revealed that in men aged 70-79 years, the ACTN3 577X allele was significantly associated with physical performance (5-m walk time, regression coefficient (β) = 0.258, P = 0.006; grip strength, β = -1.062, P = 0.012; Up and Go test time β = 0.368, P = 0.019). In women aged 70-79 years, a significant association between the ACTN3 577X allele and the FI-Lab score was observed, with a regression coefficient of β = 0.019 (P = 0.003). These findings suggest an age- and gender-specific X-additive model of R577X for 5-m walk time, grip strength, Up and Go Test time, and FI-Lab score. The ACTN3 577X allele is associated with an age- and sex-specific decrease in physical performance and an increase in frailty in an older population.

Role of selected polymorphisms in determining muscle fiber composition in Japanese men and women.

Genetic polymorphisms and sex differences are suggested to affect muscle fiber composition; however, no study has investigated the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences. Therefore, the present study examined the effects of genetic polymorphisms on muscle fiber composition with respect to sex differences in the Japanese population. The present study included 211 healthy Japanese individuals (102 men and 109 women). Muscle biopsies were obtained from the vastus lateralis to determine the proportion of myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa, and MHC-IIx). Moreover, we analyzed polymorphisms in α-actinin-3 gene (ACTN3; rs1815739), angiotensin-converting enzyme gene (ACE; rs4341), hypoxia-inducible factor 1 α gene (rs11549465), vascular endothelial growth factor receptor 2 gene (rs1870377), and angiotensin II receptor, type 2 gene (rs11091046), by TaqMan single-nucleotide polymorphism genotyping assays. The proportion of MHC-I was 9.8% lower in men than in women, whereas the proportion of MHC-IIa and MHC-IIx was higher in men than in women (5.0 and 4.6%, respectively). Men with the ACTN3 RR + RX genotype had a 4.8% higher proportion of MHC-IIx than those with the ACTN3 XX genotype. Moreover, men with the ACE ID + DD genotype had a 4.7% higher proportion of MHC-I than those with the ACE II genotype. Furthermore, a combined genotype of ACTN3 R577X and ACE insertion/deletion (I/D) was significantly correlated with the proportion of MHC-I (r = −0.23) and MHC-IIx (r = 0.27) in men. In contrast, no significant correlation was observed between the examined polymorphisms and muscle fiber composition in women. These results suggest that the ACTN3 R577X and ACE I/D polymorphisms independently affect the proportion of human skeletal muscle fibers MHC-I and MHC-IIx in men but not in women.NEW & NOTEWORTHY In men, the RR + RX genotype of the α-actinin-3 gene (ACTN3) R577X polymorphism was associated with a higher proportion of myosin heavy chain (MHC)-IIx. The ID + DD genotype of the angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism, in contrast to a previous finding, was associated with a higher proportion of MHC-I in men. In addition, the combined genotype of these polymorphisms was correlated with the proportion of MHC-I and MHC-IIx in men. Thus ACTN3 R577X and ACE I/D polymorphisms influence the muscle fiber composition in Japanese men.

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

BackgroundStudies 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.MethodsWe 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.ResultsThere 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.ConclusionsThus, 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.

ASSOCIATION OF ACTN3 R577X AND ACE I/D POLYMORPHISMS IN BRAZILIANS WRESTLERS

ABSTRACT Introduction: By associating genetics and sport, it is possible to identify subjects with greater capacity to adapt to training, and lower chances of injury. Objective: The investigation evaluated the genotypic and allelic distribution of ACTN3 R577X and ACE I/D polymorphisms in Brazilian high-performance athletes in wrestling and percussion combat sports. Methods: The study included 37 male athletes ranked from first to third place in world scenarios, divided into two groups: wrestling (23 wrestlers, being 11 of Judo, 4 of Greco-Roman style, 8 of Brazilian Jiu Jitsu, with mean age of 27.3 ± 6.9 years) and percussion combat sports (14 athletes with a mean age of 25.7±4.4 years, being 6 of Karate, 3 of Muay Thai, 4 of Taekwondo, 1 Boxing). Genotyping of ACTN3 and ACE I/D polymorphisms was performed by polymerase chain reaction (PCR) from the genomic DNA. Genotypic and allelic distributions were compared with control populations and athletes by Chi-square test and Fisher’s exact test; all analyzes considered p ≤ 0.05. Results: The genotypic distributions and allelic frequencies of ACTN3 RR=46%, RX=38% and XX=16%; R=65% and X=35%, and ACE I/D DD=47.7%, ID=34.3% and II=20%; D=62.9% and I=37.1% did not differ from the control population; however, when compared with wrestling athletes a significant difference was observed. Conclusion: These results suggest an association of ACTN3 R577X and ACE I/D genes with Brazilian high-performance wrestling athletes.

Effects of the ACTN3 R577X Genotype on the Muscular Strength and Range of Motion Before and After Eccentric Contractions of the Elbow Flexors.

The purpose of present study was to examine the association between ACTN3 R577X genotype and functional characteristics of elbow flexors before and after isokinetic eccentric contractions (ECCs). Fifty-two men (age: 20.8±3.8 years, height: 172.5±5.9 cm, body mass: 64.7±6.5 kg, BMI: 21.7±1.7) who had not participated in any regular resistance training for at least 1 year prior to this study were recruited. ECCs consisted of five sets of six maximal voluntary isokinetic (30°/s) ECCs of the elbow flexors with a range of motion (ROM) from 90° flexion to 0° (full extension). Measurements of maximal voluntary isometric contraction (MVC) torque, ROM, and muscle soreness were taken before, immediately after, and 1, 2, 3, and 5 days after ECCs. Genotyping results were analyzed for identifying ACTN3 R577X polymorphism (rs1815739) using TaqMan approach. The genotype frequencies of the ACTN3 R577X polymorphism were RR 26.9% (n=14), RX 50.0% (n=26), and XX 23.1% (n=12). There were no significant differences in MVC torque, ROM, and soreness between three genotype groups of ACTN3 R577X. However, MVC at baseline was greater in RR homozygotes than in X-allele carriers (combined XX and RX; p<0.05). ROM in RR homozygotes at baseline was lower than that of X-allele carriers. Although a significant decrease in ROM was observed in X-allele carriers until 3 days after ECCs, a significant ROM reduction in RR homozygotes was observed only immediately after ECCs. Our data indicated that ACTN3 RR genotype has higher MVC and lower flexibility than X-allele carriers at baseline, but the effect of ACTN3 R577X genotype on these two parameters is limited after ECCs.

Association analysis of the ACTN3 R577X polymorphism with passive muscle stiffness and muscle strain injury.

Passive muscle stiffness is considered to be a major factor affecting joint flexibility and is thought to relate to the occurrence of muscle strain injury. In skinned muscle fiber experiments, the R577X polymorphism of the α-actinin-3 gene (ACTN3) has been associated with passive muscle stiffness. Our primary purpose was to clarify whether the ACTN3 R577X polymorphism influences passive stiffness of human muscle in vivo. We also examined whether the ACTN3 R577X polymorphism is associated with the occurrence of hamstring strain injury. Seventy-six healthy young male subjects were genotyped for the ACTN3 R577X (rs1815739) polymorphism. Shear modulus (an index of stiffness) of each hamstring muscle (biceps femoris, semitendinosus, and semimembranosus) was assessed using ultrasound shear wave elastography, and history of hamstring strain injury was collected via a questionnaire. The muscle shear moduli of the semitendinosus and semimembranosus were significantly higher in R-allele (RR+RX genotype) carriers than in XX genotype carriers, whereas the shear modulus of the biceps femoris did not differ among the ACTN3 R577X genotypes. Frequency of past hamstring strain injury also did not differ between the 3 genotypes nor between the R-allele and XX genotype carriers. This study indicates that RR and RX genotypes of the ACTN3 R577X polymorphism (corresponding to the presence of α-actinin-3 in type II muscle fibers) are associated with increased passive muscle stiffness of the human hamstring in vivo. However, this altered mechanical property might not affect the risk of hamstring muscle strain injury.

Two genetic loci associated with ankle injury.

Ankle injuries, including sprains, strains and other joint derangements and instability, are common, especially for athletes involved in indoor court or jumping sports. Identifying genetic loci associated with these ankle injuries could shed light on their etiologies. A genome-wide association screen was performed using publicly available data from the Research Program in Genes, Environment and Health (RPGEH) including 1,694 cases of ankle injury and 97,646 controls. An indel (chr21:47156779:D) that lies close to a collagen gene, COL18A1, showed an association with ankle injury at genome-wide significance (p = 3.8x10-8; OR = 1.99; 95% CI = 1.75–2.23). A second DNA variant (rs13286037 on chromosome 9) that lies within an intron of the transcription factor gene NFIB showed an association that was nearly genome-wide significant (p = 5.1x10-8; OR = 1.63; 95% CI = 1.46–1.80). The ACTN3 R577X mutation was previously reported to show an association with acute ankle sprains, but did not show an association in this cohort. This study is the first genome-wide screen for ankle injury that yields insights regarding the genetic etiology of ankle injuries and provides DNA markers with the potential to inform athletes about their genetic risk for ankle injury.

Genes’ Polymorphisms Related To Athletic Physical Performance

Genetic predisposition has a substantial role in the development of athletic physical performance and is characterized by a large number of gene polymorphisms and the interaction of these variations. PURPOSE: (1) to examine the prevalence of genotypes of 6 genes related to physical performance (ACE I/D, ACTN3 R577X, PPARGC1A Gly482Ser,AGT Met235Thr, AMPD1 Gln12Ter, NOS3786C/T) in Estonian elite athletes; (2) to compare the distribution of gene variations between representatives of 2 sports groups (predominantly endurance-oriented and mostly for speed and/or power-oriented sports groups). METHODS: the study group consisted of 130 elite athletes (23 females and 107 males); current and former Estonian national team members; in age range 28.3±5.6 years; involved in 19 different sports disciplines. There were 77 representatives of endurance-oriented sports (17 females and 60 males) and 53 representatives of speed and power-oriented sports (6 females and 47 males). 26 athletes of the study group were medallists or finalists in the Olympic Games, World or European championships. Peripheral venous blood samples were collected for DNA extraction and genotyping (6 candidate genes) from all study subjects. For statistical analysis, a descriptive analysis and χ2 test were used to determine significant differences between the frequencies of gene variations. P-values of ≤ 0.05 were set as statistically significant. RESULTS: the higher prevalence of the RR genotype of the ACTN3 gene among athletes of endurance-oriented sports compared to athletes of speed and power-oriented sports was statistically significant (p=0.025). We did not find any significance in the distribution of other gene variations between the two sports groups. We observed the trend of a higher prevalence of the NOS3 TT genotype (p=0.076) and a lower prevalence of the AMPD1 TT genotype (p=0.09) in the endurance-oriented sports group compared to the speed and power-oriented sports group, but it was not statistically significant. CONCLUSIONS: our study results reveal a significantly higher prevalence of the ACTN3 RR genotype in athletes of the endurance-oriented sports group, which is in accordance with our previous study among young skiers and this may be an advantage for the explosive speed and power capacity in endurance sports.