Progressive strength training can reverse sarcopenia stage in middle-aged and older adults regardless of their genetic profile.

The aim of this study was to verify the association of the ACTN3-R577X polymorphism with sarcopenia stage, according to the Revised European Consensus on the Definition and Diagnosis of Sarcopenia, in middle-aged and older adults, pre- and post- ST. In the 12-week longitudinal study, 71 middle-aged and older adults were evaluated; the participants were assigned to either control or intervention group. The intervention group underwent progressive ST three times a week. All participants underwent blood collection, DNA extraction, genotyping of the ACTN3-R577X polymorphism, anthropometric evaluations, and diagnostic tests for sarcopenia. The last two tests were repeated after 12 weeks. No association of the ACTN3-R577X polymorphism with sarcopenia stage was observed before and after 12 weeks. However, the intervention group remained non-sarcopenic (n = 25, p <0.05) or achieved changes in sarcopenia stage (from sarcopenic to non-sarcopenic) (n = 13, p <0.05). Our study demonstrates that progressive ST performed regularly can reverse or prevent sarcopenia regardless of genotype for the ACTN3-R577X polymorphism.

Slow or fast: Implications of myofibre type and associated differences for manifestation of neuromuscular disorders.

Many neuromuscular disorders can have a differential impact on a specific myofibre type, forming the central premise of this review. The many different skeletal muscles in mammals contain a spectrum of slow- to fast-twitch myofibres with varying levels of protein isoforms that determine their distinctive contractile, metabolic, and other properties. The variations in functional properties across the range of classic 'slow' to 'fast' myofibres are outlined, combined with exemplars of the predominantly slow-twitch soleus and fast-twitch extensor digitorum longus muscles, species comparisons, and techniques used to study these properties. Other intrinsic and extrinsic differences are discussed in the context of slow and fast myofibres. These include inherent susceptibility to damage, myonecrosis, and regeneration, plus extrinsic nerves, extracellular matrix, and vasculature, examined in the context of growth, ageing, metabolic syndrome, and sexual dimorphism. These many differences emphasise the importance of carefully considering the influence of myofibre-type composition on manifestation of various neuromuscular disorders across the lifespan for both sexes. Equally, understanding the different responses of slow and fast myofibres due to intrinsic and extrinsic factors can provide deep insight into the precise molecular mechanisms that initiate and exacerbate various neuromuscular disorders. This focus on the influence of different myofibre types is of fundamental importance to enhance translation for clinical management and therapies for many skeletal muscle disorders.

Prevalence of Polymorphism and Post-Training Expression of ACTN3 (R/X) and ACE (I/D) Genes in CrossFit Athletes.

BACKGROUND: CrossFit is known as a functional fitness training high-intensity exercise to improve physical performance. The most studied polymorphisms are the ACTN3 R577X gene, known for speed, power, and strength, and ACE I/D, related to endurance and strength. The present investigation analyzed the effects of training on ACTN3 and ACE gene expression in CrossFit athletes for 12 weeks. METHODS: the studies included 18 athletes from the Rx category, where ACTN3 (RR, RX, XX) and ACE (II, ID, DD) characterization of genotypes and tests of maximum strength (NSCA), power (T-Force), and aerobic endurance (Course Navette) were performed. The technique used was the reverse transcription-quantitative PCR real-time polymerase chain reaction (RT-qPCR) for the relative expression analysis. RESULTS: the relative quantification (RQ) values for the ACTN3 gene increased their levels 2.3 times (p = 0.035), and for ACE, they increased 3.0 times (p = 0.049). CONCLUSIONS: there is an overexpression of the ACTN3 and ACE genes due to the effect of training for 12 weeks. Additionally, the correlation of the expression of the ACTN3 (p = 0.040) and ACE (p = 0.030) genes with power was verified.

Association between ACTN3 R577x and the physical performance of Chinese 13 to 15-year-old elite and sub-elite football players at different positions.

The purpose of this study was to investigate the prevalence of ACTN3 polymorphisms in Chinese elite and sub-elite football players aged 13-15 years at different positions. Specifically we explored whether ACTN3 genotypes were linked with athletic performance of elite and sub-elite players at different positions. The RR genotype frequency of elite defenders (p = 0.018) and midfielders (p = 0.008) was significantly higher than that of sub-elite XX genotype in elite players. Furthermore, the R allele frequency of elite defenders (p = 0.003) and midfielders (p = 0.008) was significantly higher than that of sub-elite players. In all subjects, RR players performed faster and exhibited more explosive power than RX or XX players. RR, RX and XX elite players' 20 m/30 m sprint, 5 × 25-m repeated sprint ability (5 × 25 m RSA), and standing long jump were stronger than sub-elite players, but there was no significant different in aerobic endurance between elite and sub-elite players at different positions. In conclusion, there were significant differences in ACTN3 genotypes and alleles between elite and sub-elite players at different positions, and the RR genotype was significantly associated with power-related athletic performance in Chinese youth football players.

Association between ACE and ACTN3 genes polymorphisms and athletic performance in elite and sub-elite Chinese youth male football players.

Background: Previous studies have shown controversial relationships between ACE I/D and ACTN3 R577x polymorphisms and athletic performance. Therefore, the aim of this study was to assess athletic performance indicators of Chinese youth male football players with different ACE and ACTN3 gene profiles. Methods and Materials: This study recruited 73 elite (26 13-year-olds, 28 14-year-olds, and 19 15-year-olds) and 69 sub-elite (37 13-year-olds, 19 14-year-olds, and 13 15-year-olds) and 107 controls (63 13-year-olds, and 44 14-year olds aged 13-15 years, all participants were of Chinese Han origin. We measured height, body mass, thigh circumference, speed, explosive power, repeat sprints ability, and aerobic endurance in elite and sub-elite players. We used single nucleotide polymorphism technology to detect controls elite and sub-elite players' ACE and ACTN3 genotypes, Chi-squared (χ 2) tests were employed to test for Hardy-Weinberg equilibrium. χ 2 tests were also used to observe the association between the genotype distribution and allele frequencies between controls and elite and sub-elite players. The differences in parameters between the groups were analyzed using one-way analysis of variance and a Bonferroni's post-hoc test, with statistical significance set at p ≤ 0.05. Results: (1) The genotype distribution of the ACE I/D and ACTN3 R577x polymorphisms in controls, elite and sub-elite football players were consistent with Hardy-Weinberg equilibrium, except for the ACE genotype distribution of sub-elite players. (2) The RR and DD genotypes were significantly different between elite and sub-elite players (p = 0.024 and p = 0.02, respectively). (3) Elite players were more likely to have the RR genotype and less likely to have the DD genotype compared with sub-elite players. (4) Both elite and sub-elite RR players' Yo-yo intermittent recovery level 1 (YYIR1) running distance was significantly longer than that of RX players (p = 0.05 and p = 0.025, respectively). However, there was no significantly different in YYIR1 running distance between elite and sub-elite RR players. (5) Elite XX players' VO2 max was significantly higher than that of RX and sub-elite players. Conclusion: These results indicate that ACE I/D and ACTN3 R577x polymorphisms are not associated with muscle power in Chinese elite and sub-elite players. The XX genotype of ACTN3 is associated with the aerobic endurance of elite players.

Genetic polymorphisms related to muscular strength and flexibility are associated with artistic gymnastic performance in the Japanese population.

This study aimed to examine how genetic polymorphisms related to muscular strength and flexibility influence artistic gymnastic performance in an attempt to identify a novel polymorphism associated with flexibility. In study 1, the passive straight-leg-raise (PSLR) score and aromatase gene CYP19A1 rs936306 polymorphism, a key enzyme for estrogen biosynthesis, were assessed in 278 individuals. In study 2, athletes (281 gymnasts and 1908 other athletes) were asked about their competition level, and gymnasts were assessed using the difficulty score (D-score) for each event. Muscular strength- (ACTN3 R577X rs1815739 and ACE I/D rs4341) and flexibility-related (ESR1 rs2234693 T/C and CYP19A1 rs936306 C/T) genetic polymorphisms were analyzed. In study 1, males with the CYP19A1 CT + TT genotype showed significantly higher PSLR scores than those with the CC genotype. In study 2, male gymnasts with the R allele of ACTN3 R577X showed a correlation with the floor, rings, vault, and total D-scores. In addition, male gymnasts with the C allele of ESR1 T/C and T allele of CYP19A1 C/T polymorphisms were correlated with the pommel horse, parallel bars, horizontal bar, and total D-scores. Furthermore, genotype scores of these three polymorphisms correlated with the total D-scores and competition levels in male gymnasts. In contrast, no such associations were observed in female gymnasts. Our findings suggest that muscular strength- and flexibility-related polymorphisms play important roles in achieving high performance in male artistic gymnastics by specifically influencing the performance of events that require muscular strength and flexibility, respectively.HighlightsEstrogen-related CYP19A1 polymorphism is a novel determinant of flexibility in males.Muscular strength- and flexibility-related polymorphisms play important roles in high performance in male artistic gymnastics.Genotypes of ACTN3 R577X, ESR1 rs2234693, and CYP19A1 rs936306 may contribute to training plan optimization and event selection in artistic gymnastics.

Association between ACTN3 R577X genotype and risk of non-contact injury in trained athletes: A systematic review.

PURPOSE: The aim of this study was to review, systematically, evidence concerning the link between the ACTN3 R577X polymorphism and the rates and severity of non-contact injuries and exercise-induced muscle damage in athletes and individuals enrolled in exercise training programs. METHODS: A computerized literature search was performed in the electronic databases PubMed, Web of Science, and SPORTDiscus, from inception until November 2020. All included studies compared the epidemiological characteristics of non-contact injury between the different genotypes of the ACTN3 R577X polymorphism. RESULTS: Our search identified 492 records. After the screening of titles, abstracts, and full texts, 13 studies examining the association between the ACTN3 genotypes and the rate and severity of non-contact injury were included in the analysis. These studies were performed in 6 different countries (Spain, Japan, Brazil, China, the Republic of Korea, and Italy) and involved a total participant pool of 1093 participants. Of the studies, 2 studies involved only women, 5 studies involved only men, and 6 studies involved both men and women. All the studies included were classified as high-quality studies (≥6 points in the Physiotherapy Evidence Database (PEDro) scale score). Overall, evidence suggests there is an association between the ACTN3 R577X genotype and non-contact injury in 12 investigations. Six studies observed a significant association between ACTN3 R577X polymorphism and exercise induced muscle damage: 2 with non-contact ankle injury, 3 with non-contact muscle injury, and 1 with overall non-contact injury. CONCLUSION: The present findings support the premise that possessing the ACTN3 XX genotype may predispose athletes to a higher probability of some non-contact injuries, such as muscle injury, ankle sprains, and higher levels of exercise-induced muscle damage.

Association of the ACTN3 rs1815739 Polymorphism with Physical Performance and Injury Incidence in Professional Women Football Players.

The p.R577X polymorphism (rs1815739) in the ACTN3 gene causes individuals with the XX genotype to be deficient in functional α-actinin-3. Previous investigations have found that XX athletes are more prone to suffer non-contact muscle injuries, in comparison with RR and RX athletes who produce a functional α-actinin-3 in their fast-twitch fibers. This investigation aimed to determine the influence of the ACTN3 R577X polymorphism on physical performance and injury incidence of players competing in the women's Spanish first division of football (soccer). Using a cross-sectional experiment, football-specific performance and epidemiology of non-contact football-related injuries were recorded in a group of 191 professional football players. ACTN3 R577X genotype was obtained for each player using genomic DNA samples obtained through buccal swabs. A battery of physical tests, including a countermovement jump, a 20 m sprint test, the sit-and-reach test and ankle dorsiflexion, were performed during the preseason. Injury incidence and characteristics of non-contact injuries were obtained according to the International Olympic Committee (IOC) statement for one season. From the study sample, 28.3% of players had the RR genotype, 52.9% had the RX genotype, and 18.8% had the XX genotype. Differences among genotypes were identified with one-way analysis of variance (numerical variables) or chi-square tests (categorical variables). Jump height (p = 0.087), sprint time (p = 0.210), sit-and-reach distance (p = 0.361), and dorsiflexion in the right (p = 0.550) and left ankle (p = 0.992) were similar in RR, RX, and XX football players. A total of 356 non-contact injuries were recorded in 144 football players while the remaining 47 did not sustain any non-contact injuries during the season. Injury incidence was 10.4 ± 8.6, 8.2 ± 5.7, and 8.9 ± 5.3 injuries per/1000 h of football exposure, without differences among genotypes (p = 0.222). Injury rates during training (from 3.6 ± 3.7 to 4.8 ± 2.1 injuries per/1000 h of training exposure, p = 0.100) and match (from 47.8 ± 9.5 to 54.1 ± 6.3 injuries per/1000 h of match exposure, p = 0.209) were also similar in RR, RX, and XX football players. The ACTN3 genotype did not affect the mode of onset, the time needed to return to play, the type of injury, or the distribution of body locations of the injuries. In summary, women football players with different genotypes of the p.R577X ACTN3 polymorphism had similar values of football-specific performance and injury incidence. From a practical perspective, the ACTN3 genotyping may not be useful to predict performance or injury incidence in professional women football players.

Absence of the Z-disc protein α-actinin-3 impairs the mechanical stability of Actn3KO mouse fast-twitch muscle fibres without altering their contractile properties or twitch kinetics.

BACKGROUND: A common polymorphism (R577X) in the ACTN3 gene results in the complete absence of the Z-disc protein α-actinin-3 from fast-twitch muscle fibres in ~ 16% of the world's population. This single gene polymorphism has been subject to strong positive selection pressure during recent human evolution. Previously, using an Actn3KO mouse model, we have shown in fast-twitch muscles, eccentric contractions at L0 + 20% stretch did not cause eccentric damage. In contrast, L0 + 30% stretch produced a significant ~ 40% deficit in maximum force; here, we use isolated single fast-twitch skeletal muscle fibres from the Actn3KO mouse to investigate the mechanism underlying this. METHODS: Single fast-twitch fibres are separated from the intact muscle by a collagenase digest procedure. We use label-free second harmonic generation (SHG) imaging, ultra-fast video microscopy and skinned fibre measurements from our MyoRobot automated biomechatronics system to study the morphology, visco-elasticity, force production and mechanical strength of single fibres from the Actn3KO mouse. Data are presented as means ± SD and tested for significance using ANOVA. RESULTS: We show that the absence of α-actinin-3 does not affect the visco-elastic properties or myofibrillar force production. Eccentric contractions demonstrated that chemically skinned Actn3KO fibres are mechanically weaker being prone to breakage when eccentrically stretched. Furthermore, SHG images reveal disruptions in the myofibrillar alignment of Actn3KO fast-twitch fibres with an increase in Y-shaped myofibrillar branching. CONCLUSIONS: The absence of α-actinin-3 from the Z-disc in fast-twitch fibres disrupts the organisation of the myofibrillar proteins, leading to structural weakness. This provides a mechanistic explanation for our earlier findings that in vitro intact Actn3KO fast-twitch muscles are significantly damaged by L0 + 30%, but not L0 + 20%, eccentric contraction strains. Our study also provides a possible mechanistic explanation as to why α-actinin-3-deficient humans have been reported to have a faster decline in muscle function with increasing age, that is, as sarcopenia reduces muscle mass and force output, the eccentric stress on the remaining functional α-actinin-3 deficient fibres will be increased, resulting in fibre breakages.

Genotype Distribution of the ACTN3 p.R577X Polymorphism in Elite Badminton Players: A Preliminary Study.

α-Actinin-3 is a protein with a structural role at the sarcomeric Z-line in skeletal muscle. As it is only present in fast-type muscle fibers, α-actinin-3 is considered a key mechanical component to produce high-intensity muscle contractions and to withstand external tension applied to the skeletal muscle. α-Actinin-3 is encoded by the gene ACTN3, which has a single-nucleotide polymorphism (p.R577X; rs1815739) that affects the expression of α-actinin-3 due to the presence of a stop codon. Individuals homozygous for the 577R allele (i.e., RR genotype) and RX heterozygotes express functional α-actinin-3, while those homozygous for the 577X (i.e., XX genotype) express a non-functional protein. There is ample evidence to support the associations between the ACTN3 genotype and athletic performance, with higher frequencies of the 577R allele in elite and professional sprint and power athletes than in control populations. This suggests a beneficial influence of possessing functional α-actinin-3 to become an elite athlete in power-based disciplines. However, no previous investigation has determined the frequency of the ACTN3 genotypes in elite badminton players, despite this sport being characterized by high-intensity actions of intermittent nature such as changes of direction, accelerations, jumps and smashes. The purpose of this study was to analyze ACTN3 R577X genotype frequencies in professional badminton players to establish whether this polymorphism is associated with elite athlete status. A total of 53 European Caucasian professional badminton players competing in the 2018 European Badminton Championships volunteered to participate in the study. Thirty-one were men (26.2 ± 4.4 years) and twenty-two were women (23.4 ± 4.5 years). Chi-squared tests were used to analyze the differences in the distribution of ACTN3 genotypes (RR, RX and XX) between categories and sexes. The ACTN3 RR genotype was the most frequent in the sample of professional badminton players (RR = 49.1%, RX = 22.6% and XX = 28.3%). None of the badminton players ranked in the world's top ten possessed the XX genotype (RX = 60%, RR = 40%). The distribution of the ACTN3 genotypes was similar between male and female professional badminton players (men: RR = 45.2%, RX = 25.8% and XX = 29.0%; women: RR = 54.5%, RX = 18.2% and XX = 27.3%; χ2 = 0.58; p = 0.750). The distribution of the ACTN3 genotypes in badminton players was different from the 1000 genome database for the European population (χ2 = 15.5; p < 0.001), with an overrepresentation of the RR genotype (p < 0.05) and an underrepresentation of the RX genotype (p < 0.01). In conclusion, the expression of functional α-actinin-3, associated with RR and RX genotypes in the ACTN3 gene may confer an advantage for reaching the status of elite athlete in badminton, and especially the world's top-ten ranking. Large-scale studies with different ethnic backgrounds are needed to confirm the association of the R allele of ACTN3 with badminton performance.

Associations of alpha-actinin-3 genotype with thigh muscle volume and physical performance in older adults with sarcopenia or pre-sarcopenia.

BACKGROUND: This cross-sectional study aimed to investigate the relationship of the ACTN3 genotype with thigh muscle volume and physical performance in older adults with sarcopenia or pre-sarcopenia. METHODS: Data from 64 older Japanese adults (mean age 74.4 ± 6.9 years, women 71.9%) with sarcopenia or pre-sarcopenia were analyzed. Sarcopenia and pre-sarcopenia were defined using the Asian Working Group for Sarcopenia. We collected oral mucosa samples to determine the ACTN3 genotype. Thigh muscle volumes were measured using magnetic resonance imaging. Physical performance was assessed using the usual and maximum gait speed, timed up and go test, and five-repetition sit-to-stand test. Muscle strength was assessed using grip strength. RESULT: The ACTN3 genotype proportions were 20.3% for RR, 51.6% for RX, and 28.1% for XX. Participants with the RR genotype showed greater thigh muscle volume/ht2 compared to those with the RX and XX ACTN3 genotypes (p < 0.05). The multiple linear regression analysis revealed that RX (p < 0.01) and XX (p < 0.01) ACTN3 genotypes, compared to RR, were associated with lower thigh muscle volume/ht2 and with age, sex (reference; men), weight and maximum walking speed. There was no significant difference between physical performance and muscle strength between the ACTN3 genotypes. CONCLUSION: The ACTN3 genotype of the X allele was associated with decreased thigh muscle volume compared to the ACTN3 genotype of RR in older adults with sarcopenia or pre-sarcopenia.

Loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation.

The protein α-actinin-3 expressed in fast-twitch skeletal muscle fiber is absent in 1.5 billion people worldwide due to homozygosity for a nonsense polymorphism in ACTN3 (R577X). The prevalence of the 577X allele increased as modern humans moved to colder climates, suggesting a link between α-actinin-3 deficiency and improved cold tolerance. Here, we show that humans lacking α-actinin-3 (XX) are superior in maintaining core body temperature during cold-water immersion due to changes in skeletal muscle thermogenesis. Muscles of XX individuals displayed a shift toward more slow-twitch isoforms of myosin heavy chain (MyHC) and sarcoplasmic reticulum (SR) proteins, accompanied by altered neuronal muscle activation resulting in increased tone rather than overt shivering. Experiments on Actn3 knockout mice showed no alterations in brown adipose tissue (BAT) properties that could explain the improved cold tolerance in XX individuals. Thus, this study provides a mechanism for the positive selection of the ACTN3 X-allele in cold climates and supports a key thermogenic role of skeletal muscle during cold exposure in humans.

Effect of ACTN3 R577X Genotype on Injury Epidemiology in Elite Endurance Runners.

The p.R577X polymorphism (rs1815739) in the ACTN3 gene causes individuals with the ACTN3 XX genotype to be deficient in functional α-actinin-3. Previous investigations have found that XX athletes are more prone to suffer non-contact muscle injuries. This investigation aimed to determine the influence of the ACTN3 R577X polymorphism in the injury epidemiology of elite endurance athletes. Using a cross-sectional experiment, the epidemiology of running-related injuries was recorded for one season in a group of 89 Spanish elite endurance runners. ACTN3 R577X genotype was obtained for each athlete using genomic DNA samples. From the study sample, 42.7% of athletes had the RR genotype, 39.3% had the RX genotype, and 18.0% had the XX genotype. A total of 96 injuries were recorded in 57 athletes. Injury incidence was higher in RR runners (3.2 injuries/1000 h of running) than in RX (2.0 injuries/1000 h) and XX (2.2 injuries/1000 h; p = 0.030) runners. RR runners had a higher proportion of injuries located in the Achilles tendon, RX runners had a higher proportion of injuries located in the knee, and XX runners had a higher proportion of injuries located in the groin (p = 0.025). The ACTN3 genotype did not affect the mode of onset, the severity, or the type of injury. The ACTN3 genotype slightly affected the injury epidemiology of elite endurance athletes with a higher injury rate in RR athletes and differences in injury location. However, elite ACTN3 XX endurance runners were not more prone to muscle-type injuries.

The ACTN3 577XX Null Genotype Is Associated with Low Left Ventricular Dilation-Free Survival Rate in Patients with Duchenne Muscular Dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a fatal progressive muscle-wasting disease caused by mutations in the DMD gene. Dilated cardiomyopathy is the leading cause of death in DMD; therefore, further understanding of this complication is essential to reduce morbidity and mortality. METHODS: A common null variant (R577X) in the ACTN3 gene, which encodes α-actinin-3, has been studied in association with muscle function in healthy individuals; however it has not yet been examined in relationship to the cardiac phenotype in DMD. In this study, we determined the ACTN3 genotype in 163 patients with DMD and examined the correlation between ACTN3 genotypes and echocardiographic findings in 77 of the 163 patients. RESULTS: The genotypes 577RR(RR), 577RX(RX) and 577XX(XX) were identified in 13 (17%), 44 (57%) and 20 (26%) of 77 patients, respectively. We estimated cardiac involvement-free survival rate analyses using Kaplan-Meier curves. Remarkably, the left ventricular dilation (> 55 mm)-free survival rate was significantly lower in patients with the XX null genotype (P < 0.01). The XX null genotype showed a higher risk for LV dilation (hazard ratio 9.04). CONCLUSIONS: This study revealed that the ACTN3 XX null genotype was associated with a lower left ventricular dilation-free survival rate in patients with DMD. These results suggest that the ACTN3 genotype should be determined at the time of diagnosis of DMD to improve patients' cardiac outcomes.

Polimorfismo genético ACTN3 R577X en deportistas universitarios chilenos / ACTN3 R577X gene polymorphism in Chilean college athletes

Uno de los principales factores genéticos que influenciarían el rendimiento muscular humano es el gen ACTN3, que codifica la proteína estructural del sarcómero α-actinina-3. El polimorfismo R577X (rs1815739) del gen ACTN3 ha sido asociado con varios indicadores de rendimiento muscular y físico en deportistas y población general, pero este fenómeno ha sido escasamente descrito en poblaciones de Latinoamérica y Chile. Por lo tanto, el objetivo del presente estudio fue describir la frecuencia genotípica y distribución alélica de los genotipos de ACTN3 R577X en deportistas universitarios chilenos. 129 deportistas universitarios chilenos representantes de diferentes selecciones deportivas (halterofilia, balonmano, voleibol, rugby, basquetbol, futbol y futsal) participaron como voluntarios. Los análisis moleculares del polimorfismo R577X del gen ACTN3 fueron realizados mediante reacción en cadena de la polimerasa (PCR) y restricción enzimática (RFLP). La distribución de genotipos del polimorfismo ACTN3 R577X fue RR: 34,8 % (n=45), RX: 50,4 % (n=65), XX: 14,7 % (n=19), y la frecuencia relativa de alelos fue R: 0,601 y X: 0,399. Además, se encontró asociación entre distribución de genotipos (c2= 12,26; 2 gl; p=0,002) y frecuencia relativa de alelos (c2= 11.02; 1 gl; p=0.0009) con el sexo de los participantes. Sin embargo, no hubo asociación al realizar análisis por tipo de deporte practicado. Los hallazgos de la presente investigación sugieren que el polimorfismo R577X del gen ACTN3 está asociado con el sexo en deportistas universitarios chilenos. Además, estos resultados describen de forma inédita la distribución genotípica y frecuencia alélica de esta variante genética en población chilena, mostrando una distribución similar a otros estudios realizados en poblaciones de deportistas en Brasil, Rusia, Estados Unidos y Turquía. No obstante, también muestra diferencias con otras poblaciones generales y de deportistas.

One of the main genetic factors that influence the muscular performance is the gene that encodes the structural protein α-actinin-3 (ACTN3). The R577X polymorphism (rs1815739) of ACTN3 has been associated with indicators of muscle and physical performance in athletes and general population, but this has been scarcely described in the Latin American and Chilean population. Thus, the aim of the present study was to describe the genotypic frequency and allelic distribution of ACTN3 R577X genotypes in college athletes. A total of 129 unrelated Chilean college athletes representing various sport disciplines (weightlifting, handball, volleyball, rugby, basketball, soccer and futsal) were volunteered for the study. ACTN3 R577X gene polymorphism was analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). For the total sample the genotypes distribution for R577X polymorphism was RR: 34.8 % (n=45), RX: 50.4 % (n=65), XX: 14.7 % (n=19), and the relative frequency of alleles was R: 0,601 and X: 0,399. Moreover, an association was found between genotype distribution (c2= 12.26; 2 df; p=0.002) and allele frequencies (c2= 11.02; 1 df; p=0.0009) with the sex of the participants. However, there were no associations when performing analysis by type of sports. These findings suggest that the R577X polymorphism of the ACTN3 gene is associated with sex in Chilean college athletes. Furthermore, these results describe in an unprecedented manner, the genotypic distribution and allelic frequency of this genetic variant in Chilean population, showing a similar distribution to other studies conducted in populations of athletes in Brazil, Russia, the United States and Turkey. However, it also shows differences with other general and athletes populations.

Relationships between the Expression of the ACTN3 Gene and Explosive Power of Soccer Players.

Muscle strength and maximal speed are factors determining athlete's results during competition. Their association with ACTN3 gene activity has been documented. The purpose of this study was the analysis of ACTN3 gene expression during a 2 month training cycle of soccer players and its correlation with the countermovement jump (CMJ) and squat jump (SJ). The study group consisted of 22 soccer players (aged 17-18). The study material included peripheral blood lymphocytes. The relative expression (RQ) of the ACTN3 gene was analyzed by qPCR and performed before and after the two-month training cycle. Before the training cycle low expression levels of ACTN3 (median RQ = 0.95) were observed, yet after the training cycle they were elevated (median RQ = 1.98) ( p = 0.003). There was an increase in performance of both jumps: SJ (p = 0.020) and CMJ (p = 0.012) at the end of the training cycle. A simultaneous increase in the ACTN3 gene expression level and height in both jump tests was observed in 73% of athletes (p > 0.05). There were no significant relationships between the ACTN3 gene expression level and the results of the CMJ and SJ. However, explosive strength is a complex feature shaped by many different factors and it could be the reason why we did not observe correlations between these variables.

ACTN3 genotype distribution across horses representing different utility types and breeds.

In horses, the identification of the genetic background of phenotypic variation, especially with regard to performance characteristics and predisposition to effort, has been extensively studied. As α-actinin-3 function is related to the regulation of muscle contraction and cell metabolism, the ACTN3 gene is considered one of the main genetic factors determining muscle strength. The aim of the present study was to assess the genotype distribution of two SNP variants within the equine ACTN3 gene (g.1104G > A and c.2334C > T) across different utility types and horse breeds. The analyses were performed on five breeds representing horses of different types, origins and utilities according to performance (in total 877 horses): primitive (Polish koniks; Hucul horses), draught (Polish heavy draught) and light (Thoroughbred and Arabian horses). Two polymorphisms within the ACTN3 gene locus were genotyped and genotype and allele frequency were compared across populations in order to verify if the identified differences contribute to the phenotypic variation observed in horse breeds. The present study allowed confirmation of the significant differences in genotype distribution of g.1104G > A localized in the promoter region between native breeds and racehorse breeds such as Thoroughbreds and Arabians. The allele/genotype variations between primitive and light breeds confirmed that the analysed variant was under selection pressure and can be correlated with racing ability. Moreover, the significant differences for the c.2334C > T genotype frequency between Arabian horses and other breeds indicate its relationship with endurance and athletic performance. The predominance of the T allele (85%) in Arabians suggests that the T variant was favoured during selection focused on improving stamina and could be one of the genetic factors determining endurance ability. Further research is needed to confirm the association of both polymorphisms with exact racing and/or riding results.

Association Between Hematological Parameters and Iron Metabolism Response After Marathon Race and ACTN3 Genotype.

α-Actinin-3 (ACTN3 R577X, rs.1815739) polymorphism is a genetic variation that shows the most consistent influence on metabolic pathway and muscle phenotype. XX genotype is associated with higher metabolic efficiency of skeletal muscle; however, the role of ACTN3 polymorphism in oxygen transport and utilization system has not yet been investigated. Therefore, the aim of this study was to determine the influence of ACTN3 polymorphisms on hematological and iron metabolism response induced by marathon race. Eighty-one Brazilian amateur male endurance runners participated in the study. Blood samples and urine were collected before; immediately after; and 1, 3, and 15 days after the marathon race. Urine, hematological parameters, iron metabolism, and ACTN3 genotyping analyses were performed. The marathon race induced a decrease in erythrocytes, Hb, and Ht, and an increase in hematuria, creatinine, myoglobin, red cell distribution width, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, direct and indirect bilirubin and erythropoietin. Moreover, an elevation immediately or 1 day after the marathon race follows a reduction 3 or 15 days after the marathon race were observed on transferrin saturation and iron and transferrin levels. Hematological parameters and iron metabolism changes induced by marathon race were not observed in XX genotypes. Hematuria and decreased erythrocytes, Hb, Ht, and iron and transferrin levels were observed only in RR and/or RX genotypes but not in XX genotypes. The percentage of runners with hematuria, leukocyturia, iron deficiency, creatinine, myoglobin, and bilirubin imbalance was higher in RR compared to XX genotypes. ACTN3 polymorphism is associated with iron metabolism and hematological responses after endurance exercise. Despite these results being based on a small sample, they highlight a protective role of the XX genotype on hematological and renal changes induced by long-distance exercise. Therefore, these findings should be further replicated.

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.