ACTN3 Research Articles

Analysis of Equine ACTN3 Gene Polymorphisms in Yili Horses

The sarcomeric protein α-actinin-3, which is encoded by the ACTN3 gene, interacts with multiple proteins involved in structure, muscle metabolism, and signaling. α-Actinin-3 deficiency caused by a knockout or mutation of the terminator sequence of the ACTN3 gene leads to a change in muscle phenotype from fast-twitch fibers to slow-twitch fibers, resulting in enhanced aerobic metabolic energy, decreased calcium sensitivity, and degraded sprint and power performance. In this study, the single-nucleotide polymorphisms (SNPs) in the equine ACTN3 gene in Yili horses (n = 38) were detected and sequenced. Comparison of the obtained equine ACTN3 sequences with those in GenBank identified 15 SNPs, with one located in the promoter, eight located in exons, and six located in introns. All eight exonic SNPs, except for the missense mutation g.9059T>G, were synonymous. The g.9059T>G mutation lead to an increase in the free energy of the thermodynamic ensemble of the equine ACTN3 mRNA from −1157.84 to −1157.35 kcal/mol and changed the secondary structure of α-actinin-3, which may affect its function. We hypothesized that g.9059T>G might affect athletic performance and may be a candidate SNP for racehorse breeding.

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.

Prevalence of alpha actinin-3 gene (ACTN3) R577X and angiotensin converting enzyme (ACE) insertion / deletion gene polymorphisms in national and amateur Turkish athletes

Studies to date showed the importance of alpha- actinin-3 (ACTN3) R577X and angiotensin converting enzyme (ACE) ID polymorphisms on determining athletic performance. Therefore, in this study, we aimed to examine polymorphisms given to Turkish athletes and compare them with sedentary individuals. Genomic DNAs were extracted from peripheral blood by using commercially available DNA isolation kit (Macherey-Nagel, NucleoSpin®, Germany). For this study, a total of 84 volunteers (23 national athletes, 27 amateur athletes and 34 sedentary controls) was recruited. ACE ID genotypes were determined by conventional polymerase chain reaction, and ACTN3 R577X polymorphisms by polymerase chain reaction- restriction fragment length polymorphism methodology. In ACTN3 R577X polymorphism, RX was the dominating genotype, and we detected no RR genotype in national athletes. (no RR genotype was detected in national athletes) X allele is more frequent in national athletes and R allele was more frequent in both amateur athletes and control group. II genotype was more frequent in national athletes and in control group, whereas DD genotype was more frequent in amateur athletes for ACE ID polymorphism. When we consider alleles, D allele was found more frequently in amateur athletes and control group whereas I allele was more frequent in national athletes in ACE ID polymorphism. For ACTN3, X allele was superior to R allele. ACTN3 R577X and ACE ID polymorphisms were important biomarkers in determining athletic performance. However, our results in Turkish athletes suggest that ACE D allele and ACTN3 X alleles may be beneficial to athletes potentially, regardless of the distance they perform.

The Effect of ACTN3 Gene Doping on Skeletal Muscle Performance

Loss of expression of ACTN3, due to homozygosity of the common null polymorphism (p.Arg577X), is underrepresented in elite sprint/power athletes and has been associated with reduced muscle mass and strength in humans and mice. To investigate ACTN3 gene dosage in performance and whether expression could enhance muscle force, we performed meta-analysis and expression studies. Our general meta-analysis using a Bayesian random effects model in elite sprint/power athlete cohorts demonstrated a consistent homozygous-group effect across studies (per allele OR = 1.4, 95% CI 1.3-1.6) but substantial heterogeneity in heterozygotes. In mouse muscle, rAAV-mediated gene transfer overexpressed and rescued α-actinin-3 expression. Contrary to expectation, invivo "doping" of ACTN3 at low to moderate doses demonstrated an absence of any change in function. At high doses, ACTN3 is toxic and detrimental to force generation, to demonstrate gene doping with supposedly performance-enhancing isoforms of sarcomeric proteins can be detrimental for muscle function. Restoration of α-actinin-3 did not enhance muscle mass but highlighted the primary role of α-actinin-3 in modulating muscle metabolism with altered fatiguability. This is the first study to express a Z-disk protein in healthy skeletal muscle and measure the invivo effect. The sensitive balance of the sarcomeric proteins and muscle function has relevant implications in areas of gene doping in performance and therapy for neuromuscular disease.

ACTN3 Genotype in Professional Sport Climbers.

Ginszt, M, Michalak-Wojnowska, M, Gawda, P, Wojcierowska-Litwin, M, Korszeń-Pilecka, I, Kusztelak, M, Muda, R, Filip, AA, and Majcher, P. ACTN3 genotype in professional sport climbers. J Strength Cond Res 32(5): 1311–1315, 2018—The functional RR genotype of the alpha-actinin-3 (ACTN3) gene has been reported to be associated with elite sprint/power athlete status. Although large and rapidly increasing number of studies have investigated the associations between the ACTN3 genotypes and athletic performance in various sport disciplines, there is a lack of studies on the genetic predisposition in sport climbing, which was selected to be part of the next Summer Olympic Games in Tokyo 2020 with three subdisciplines (“lead climbing,” “speed climbing,” and “bouldering”). The aim of the study is to determine the frequency distribution of ACTN3 genotypes and alleles in professional lead climbers and boulderers. 100 professional sport climbers from Poland, Russia, and Austria were divided into 2 equal groups: professional boulderers and professional lead climbers were involved in the study. ACTN3 allele frequencies and genotypes were compared with 100 sedentary controls. Genotypes were determined using polymerase chain reaction–restriction fragment length polymorphism method. The percent distribution of RR genotype in the boulderers was significantly higher than in lead climbers and controls (62 vs. 26%; 33%, respectively; χ2 = 17.230, p = 0.0017). The frequencies of ACTN3 R allele in boulderers differed significantly from lead climbers and controls (77 vs. 51%; 58%, respectively; χ2 = 15.721, p = 0.0004). The proportion of the ACTN3 RR genotype is significantly higher in boulderers than in lead climbers and may be related to the specific type of predisposition to this subdiscipline.

Association of ACE ID and ACTN3 C>T genetic polymorphisms with response to a multicomponent training program in physical performance in women from 50 to 70 years

Summary Objective This study examined the effects of ACE ID and ACTN3 C>T in response to a multicomponent training program on power and strength levels, aerobic endurance and agility in women from 50 to 70 years. Methods The multicomponent training program was performed for 12 weeks, twice a week and each training session lasted 90 min. Results Regarding the ACE gene, the three groups improved performance in all tests, with the exception of the DD group in the sit to stand test and the ID group in the 6 minutes-walking test. Regarding the ACTN3 gene, the three groups improved performance in all tests, with the exception of the TT group in the sit to stand test and the CC group in the six minutes walking test.

Is training‐induced increase in muscle mass influenced by ACTN3 genotype?

INTRODUCTIONAlpha‐actinin‐3 is a skeletal muscle specific protein. A polymorphism in the ACTN3 gene (R577X) results in lack of alpha‐actinin‐3 protein in skeletal muscle of individuals with XX‐genotype. In sprint/power oriented elite athletes the prevalence of the X‐allele is much lower than in control populations, implying that lack of alpha‐actinin‐3 is detrimental for these athletes. The mechanistic link, however, is not fully established. Actn3 knock‐out mice are shown to have lower muscle mass. We have previously reported that humans with XX‐genotype have lower activation of mTOR‐signaling pathway in response to acute sprint exercise. This may indicate that the XX‐genotype is associated with an attenuated skeletal muscle hypertrophy in response to exercise. The aim of the present study was to examine the impact of ACTN3 genotype on hypertrophy signaling in skeletal muscle and on training‐induced increase in muscle mass.METHODS69 male and female subjects participating in five different longitudinal training studies with different training conditions were investigated. 20 subjects performed 5 weeks of supervised progressive knee‐extensor resistance training (study 1), 16 subjects performed 8 weeks of the same resistance training but with intervention by oral intake of acetylic acid (study 2) and 19 subjects performed 10 weeks of combined leg‐press and knee‐extensor resistance training with one leg (study 3a) followed by a detraining period and a new 5 weeks of the same resistance training but with both legs (pre‐trained leg (study 3b) and previously untrained leg (study 3c)). The volume of m. quadriceps, before and after the training periods, was assessed by MRI (study 1 and 2) or ultrasonography (study 3a, 3b and 3c). Muscle samples obtained in connection with an acute exercise bout in each study were analyzed for phosphorylation of p70S6k by western blot. DNA was extracted from muscle samples and genotyping for the R577X polymorphism was performed by allelic discrimination.RESULTSThe mean relative increase in muscle volume with training was (mean ±SD) 9.7 ±6 % and there was no significant difference between the studies. Therefore the impact of ACTN3 genotype on the training‐induced increase in muscle mass was analyzed in pooled data from all five studies. The relative increase in muscle volume in the different ACTN3 genotypes was (mean ±SD) 10.5 ±6 % in RR, 9.4 ±5 % in RX and 8.4 ±6 % in XX. The acute‐exercise induced increase in relative phosphorylation of p70S6k was (mean ±SD) 25 ±36 % in RR, 14 ±25 % in RX and 10 ±7% in XX. The observed differences between ACTN3‐genotypes were found to be not statistically significant.CONCLUSIONDespite the fact, that the relative increase in muscle volume and phosphorylation of p70S6k was numerically lower in the XX‐genotype as compared to RR and RX, there were no statistically significant differences between the genotypes. Our hypothesis, that ACTN3 genotype is a genetic modifier important for regulation of muscle mass, could thus not be confirmed by a present investigation. A type 2 error cannot be excluded, however, due to, the in general, low relative increase in muscle volume by this type of intervention.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Differences in muscle strength, muscle soreness, and blood CK activity after eccentric exercise for ACTN3 gene polymorphism

[Purpose] The purpose of this study was to examine the change of muscle damage markers after maximal eccentric exercise and to verify the difference of recovery according to ACTN3 gene polymorphism. [Methods] Fifty healthy males participated in this study. Subjects performed 25 times/1 set (total 2 set) maximal eccentric contractions of the elbow flexor muscles on a modified preacher curl machine with a between-sets rest time of 5 min. Maximal isometric contraction (MIC) was measured 6 times (pre, post, after 24 h, 48 h, 72 h and 96 h). Muscle soreness (SOR) was measured 5 times (pre, after 24 h, 48 h, 72 h and 96 h). Blood samples were collected 5 times (pre, after 24 h, 48 h, 72 h and 96 h). ACTN3 gene polymorphisms were identified using polymerase chain reaction (PCR). Data were analyzed using a 2-way repeated measure ANOVA and post hoc Bonferroni test. [Results] Analysis of ACTN3 gene polymorphism revealed the following distribution: 22% RR (n=11), 50% RX (n=25), and 28% XX (n=14). Individuals were classified into the RR homozygote group (n=11) and the X-allele group (n=39). MIC showed a significant difference between groups and interaction (p<.05). The groups differed significantly in MIC at 48 h, 72 h, and 96 h after exercise and the X-allele group decreased more than the RR homozygote group. The groups differed significantly in muscle soreness and interaction (p<.05). SOR in the X-allele group was significantly higher than in the RR homozygote group at 24 h after exercise. Although blood CK activity was lower in the RR homozygote group than in the X-allele group, but there was no significant difference between the groups (p>.05). [Conclusion] The RR homozygote group showed lower muscle strength reduction rate, muscle soreness and blood CK activity than the X-allele group. This indicates that RR individuals have a lower risk of exercise-induced muscle damage than those with an X-allele.

Influence of ACTN3 R/X gene polymorphisms on racing strategy in rowing athletes

This study compared the polymorphisms RR, XX and RX of the ACTN3 gene among rowers with different race strategies across competitive levels and weight categories. We evaluated 137 rowers divided into: male non-elite openweight (n = 23), male elite openweight (n = 33), male non-elite lightweight (n = 31), male elite lightweight (n = 13), female non-elite openweight (n = 9), female elite openweight (n = 9) and female non-elite lightweight (n = 15), female elite lightweight (n = 4). The main results indicated that rowers who adopted starting/early (within the initial 500 m) or finishing/late (within the final 500 m) strategies exhibited similar ACTN3 genotype frequencies, while fewer athletes who adopted moderate (within the middle 1000 m) pacing strategies were categorised with the ACTN3 XX (8%) genotype as compared to the RR (50%) and RX (42%) genotypes (p = 0.002). Elite openweight male rowers with the ACTN3 RR more frequently preferred moderate pacing strategies (p = 0.006), while non-elite lightweight male athletes with ACTN3 RR more frequently preferred starting/early pacing strategies (p ≤ 0.001). Therefore, rowing athletes with specific ACTN3 genotypes may adopt unique race pacing strategies, while no differences were shown by competitive level or weight category.

ENPP1 and ESR1 genotypes associated with subclassifications of craniofacial asymmetry and severity of temporomandibular disorders

We investigated whether ACTN3, ENPP1, ESR1, PITX1, and PITX2 genes which contribute to sagittal and vertical malocclusions also contribute to facial asymmetries and temporomandibular disorders (TMD) before and after orthodontic and orthognathic surgery treatment. One hundred seventy-four patients with a dentofacial deformity were diagnosed as symmetric or subdivided into 4 asymmetric groups according to posteroanteriorcephalometric measurements. TMD examination diagnosis and jaw pain and function (JPF) questionnaires assessed the presence and severity of TMD. Fifty-two percent of the patients were symmetric, and 48% were asymmetric. The asymmetry classification demonstrated significant cephalometric differences between the symmetric and asymmetric groups, and across the 4 asymmetric subtypes: group 1, mandibular body asymmetry; group 2, ramus asymmetry; group 3, atypical asymmetry; and group 4, C-shaped asymmetry. ENPP1 SNP-rs6569759 was associated with group 1 (P=0.004), and rs858339 was associated with group 3 (P=0.002). ESR1 SNP-rs164321 was associated with group 4 (P=0.019). These results were confirmed by principal component analysis that showed 3 principal components explaining almost 80% of the variations in the studied groups. Principal components 1 and 2 were associated with ESR1 SNP-rs3020318 (P<0.05). Diagnoses of disc displacement with reduction, masticatory muscle myalgia, and arthralgia were highly prevalent in the asymmetry groups, and all had strong statistical associations with ENPP1 rs858339. The average JPF scores for asymmetric subjects before surgery (JPF, 7) were significantly higher than for symmetric subjects (JPF, 2). Patients in group 3 had the highest preoperative JPF scores, and groups 2 and 3 were most likely to be cured of TMD 1year after treatment. Posteroanterior cephalometrics can classify asymmetry into distinct groups and identify the probability of TMD and genotype associations. Orthodontic and orthognathic treatments of facial asymmetry are effective at eliminating TMD in most patients.

The Effect Of ACTN3 Genotype On Self-reported One-mile Running Time In Young, Recreationally Active Women

Alpha-actinins form a crosslink between actin filaments and adjacent sarcomeres, and play a role in signaling and energy metabolism. Alpha-actinin-3, is encoded by the ACTN3 gene and only presents in Type II muscle fibers. Homozygosity for the 577X allele (XX) results in complete deficiency of α-actinin-3 and a compensatory upregulation of α-actinin-2, whereas heterozygosity (RX) and homozygosity for the 577R allele (RR) provide for the production of α-actinin-3. Research has reported a greater proportion of elite female distance runners are homozygous for the 577X allele compared to controls. However, no study to date has examined that apparent relationship in recreational women runners. PURPOSE: To examine the effect of ACTN3 genotype on self-reported one-mile running personal records (PR) in young, recreationally active women. METHODS: Thirty nine participants, grouped by the presence (RR+RX: n=27, age: 21.7 ± 3.8 years, BMI: 22.9 ± 3.3 kg/m2) or absence (XX: n=12, age: 21.2 ± 3.2 years, BMI: 21.5 ± 1.8 kg/m2) of the 577R allele, reported one-mile running PR. Genotype effects were examined using independent-sample t-tests and magnitude-based inference (MBI). RESULTS: A trend (p=0.065) toward faster one-mile times was observed in XX genotypes (415.7 ± 78.9 s) when compared to the RR+RX group (480.3 ± 104.8 s). MBI revealed a mechanistically beneficial effect of XX genotype (mean difference; ± 90% CI; -65 s, ± 57 s). Similar observations were made among a subset of thirteen faster runners, who reported a one-mile PR of less than seven minutes (RR+RX: n=7, age: 21.9 ± 5.0 years, BMI: 20.9 ± 3.4 kg/m2; XX: n=6, age: 19.5 ± 0.5 years; BMI: 21.8 ± 1.5 kg/m2). Though not statistically significant (p=0.378), those in the XX group (355.8 ± 46.5 s) reported 5.4% faster times than those in the RR+RX group (376.3 ± 33.6 s). MBI revealed a mechanistically beneficial effect of XX genotype (-20 s; ± 40 s). CONCLUSION: These findings suggest a potential benefit of XX genotype on middle-distance endurance performance. This is in agreement with prior investigations that have linked XX genotype to endurance capabilities in elite female athletes.

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.

R577X polymorphism of alpha-actinin-3 in human populations of North-Eastern Asia

Background. In polymorphism rs1815739, a C T transition converts arginine to a premature stop-codon at residue 577 of the alpha-actinin-3 (ACTN3) protein (R577X polymorphism). This polymorphism may affect muscle performance, and the derived 577X allele has been found to be under-represented in sprint/power athletes. In addition, loss of alpha-actinin-3 results in a shift in muscle metabolism toward the more efficient aerobic pathway, thus pointing that this polymorphism may have been involved in enhancing the capability for hunting and for cold adaptation. Here, we study rs1815739 polymorphism in native populations (Chukchi, Koryaks and Evens) and newcomers (Russians) of North-Eastern Asia.&#x0D; Materials and methods. Genomic DNA was isolated from peripheral blood. ACTN3 genotypes for rs1815739 locus were established by enzymatic digestion of amplicons with DdeI. Heterozygotes TT were confirmed by DNA sequencing. In addition, data on exome variation in Siberian populations were analyzed.&#x0D; Results. Lowered frequencies (less than 40%) of mutant allele rs1815739-T were found in studied populations of North-Eastern Asia. Analysis of exome data has shown that haplotype comprising the rs1815739-T allele reaches the highest frequencies in populations of Southern and Central Siberia, while it is rather rare in the north-east of Siberia.&#x0D; Conclusion. The results obtained contradict the hypothesis that the rs1815739 polymorphism may have been involved in cold adaptation of North-East Siberians.

ACTN3 genotype influences exercise-induced muscle damage during a marathon competition

Exercise-induced muscle damage has been identified as one of the main causes of the progressive decrease in running and muscular performance in marathoners. The aim of this investigation was to determine the influence of the ACTN3 genotype on exercise-induced muscle damage produced during a marathon. Seventy-one experienced runners competed in a marathon race. Before and after the race, a sample of venous blood was obtained and maximal voluntary leg muscle power was measured during a countermovement jump. In the blood samples, the ACTN3 genotype (R577X) and the changes in serum creatine kinase and myoglobin concentrations were measured. Data from RX heterozygotes and XX mutant homozygotes were grouped as X allele carriers and compared to RR homozygotes. At the end of the race, X allele carriers presented higher serum myoglobin (774 ± 852 vs 487 ± 367 UL-1; P = 0.02) and creatine kinase concentrations (508 ± 346 vs 359 ± 170ngmL-1; P = 0.04) than RR homozygotes. Pre-to-post-race maximal voluntary leg muscle power reduction was more pronounced in X allele carriers than RR homozygotes (-34.4 ± 16.1 vs -27.3 ± 15.4%; P = 0.05). X allele carriers self-reported higher levels of lower limb muscle pain (7 ± 2 vs 6 ± 2cm; P = 0.02) than RR homozygotes at the end of the race. In comparison to RR homozygotes, X allele carriers for the R577X polymorphism of the ACTN3 gene presented higher values for typical markers of exercise-induced muscle damage during a competitive marathon. Thus, the absence of a functional α-actinin-3 produced by the X allele might induce higher levels of muscle breakdown during prolonged running events.

ACTN3 polymorphism prevalence in general population of six Balkan countries

The aim of this study was to investigate the prevalence of RR, RX and XX genotypes of rs1815739 single nucleotide polymorphism of ACTN3 gene in general population of six Balkan countries. This SNP is currently thought to give genetic predisposition for advantageous sport performance, with its R allele positively correlating with better performance in strength/power sports, and X allele being present in higher frequency in elite athletes in endurance disciplines. A total of 483 individuals (281 males and 202 females) from seven populations from six countries was tested. Samples were collected by buccal swabbing method, DNA was isolated according to salting-out protocol and genotyping was performed using PCR and RFLP analysis. Obtained results suggest that RR and RX genotypes (43.7% and 44.1%, respectively) are overrepresented when compared to XX genotype (12.2%). The XX genotype in the study samples is present in lower frequency when compared to the global (16-18%) and European (18%) average. This study reports the first population data on genotype prevalence in sports-related genes for this part of Europe and is the beginning of research interests that intend to investigate genetic predispositions of elite athletes from this region competing internationally in different disciplines.

ACTN3 X-allele carriers had greater levels of muscle damage during a half-ironman.

Alpha-actinin-3, encoded by the ACTN3 gene, is an actin-binding protein with an important role in myofibril contraction and muscle force output. In humans, there is a relatively common deficiency of the α-actinin-3 due to homozygosity in a polymorphism of the ACTN3 gene (R577X, rs1815739), that has been related to decreased resistance to strain during voluntary muscle contractions. The purpose of this study was to investigate the influence of the ACTN3 genotype on the level of exercise-induced muscle damage attained by 23 experienced triathletes during an official half-ironman competition. Before and after the race, a sample of venous blood was obtained and jump height was measured during a countermovement jump. The changes in serum creatine kinase (CK-MM isoform) were measured in the blood samples and muscle pain was measured with a visual analogue scale (0-10cm). Data from RX heterozygotes and XX mutant homozygotes were grouped as X-allele carriers (n=13) and compared to RR homozygotes (n=10). Race time was very similar between groups (313±31 vs. 313±25min; P=0.45); however, pre-to-post-competition reduction in jump height was greater in X-allele carriers than RR homozygotes (-18.4±11.4 vs. -8.2±6.9%; P=0.04). At the end of the race, X-allele carriers presented higher serum CK-MM concentrations (682±144 vs. 472±269U/L; P=0.03), and there was also a tendency for higher self-reported values of lower limb muscle pain (7.7±1.1 vs. 6.3±2.3cm; P=0.06). X-allele triathletes in the ACTN3 R577X polymorphism presented greater signs of exercise-induced muscle damage during a half-ironman race than RR homozygotes.

ACTN3 R577X genotype and performance of elite middle-long distance swimmers in China.

The ACTN3 gene is one of the genes that have a potential influence on physical performance. Studies have shown that the 577R genotype of ACTN3 is more prevalent in sprint athletes, while the 577X genotype is more prevalent in endurance athletes. In swimming, both power and endurance related phenotypes are equally needed for swimmers to excel at the elite level. Therefore, the ACTN3 R577X polymorphism may become a genetic marker for swimmers. The study aimed to examine the association of the ACTN3 R577X genotype with the performance of elite middle-long distance (MLD) swimmers. The distributions of the ACTN3 R577X (rs1815739) genotype and allele were examined in a general population (206) and a group of elite MLD swimmers (160) in China by using PCR-RFLP and TOF. Compared with the general population, the elite MLD swimmers, especially the females, had a higher frequency of the RR genotype. The swimmers had a higher frequency of the R allele than the general population. However, the difference was not statistically significant. After being stratified by performance, the difference of the R allele frequency between the international master athletes and the general population was statistically significant. The elite MLD swimmers had a higher frequency of the RR genotype than the RX+XX genotype compared with the general population. The ACTN3 R577X polymorphism was associated with the performance of elite MLD swimmers in China. The SNP R577X could be used as a biomarker for selecting elite MLD swimmers in China.

Genetic characterization of physical activity behaviours in university students enrolled in kinesiology degree programs.

Studies of physical activity behaviours have increasingly shown the importance of heritable factors such as genetic variation. Nonsynonymous polymorphisms of alpha-actinin 3 (ACTN3) and the β-adrenergic receptors 1 and 3 (ADRB1 and ADRB3) have been previously associated with exercise capacity and cardiometabolic health. We thus hypothesized that these polymorphisms are also related to physical activity behaviours in young adults. To test this hypothesis we examined relationships between ACTN3 (R577X), ARDB1 (Arg389Gly), ADRB3 (Trp64Arg), and physical activity behaviours in university students. We stratified for student enrollment in kinesiology degree programs compared with nonmajors as we previously found this to be a predictor of physical activity. We did not identify novel associations between physical activity and ACTN3. However, the minor alleles of ADRB1 and ADRB3 were significantly underrepresented in kinesiology students compared with nonmajors. Furthermore, carriers of the ADRB1 minor allele reported reduced participation in moderate physical activity and increased afternoon fatigue compared with ancestral allele homozygotes. Together, these findings suggest that the heritability of physical activity behaviours in young adults may be linked to nonsynonymous polymorphisms within β-adrenergic receptors.

ACTN3 Gene R577X Polymorphism Associated with High-Density Lipoprotein Cholesterol and Adiponectin in Rugby Players

To determine the relationship between the R577X polymorphism of the α-actinin-3 (ACTN3), which may play a role in the individual differences observed in the effects of exercise on health benefits and antiatherogenic markers (i.e., high-density lipoprotein cholesterol [HDL-C] and adiponectin) in athletes. Seventy-six male rugby players (mean age 19.8 years) were enrolled in this study. Genomic DNA was extracted from peripheral blood samples, and restriction fragment length polymorphism-polymerase chain reactions were conducted to assess ACTN3 genotypes. Body mass index (BMI), waist circumference, serum lipids including HDL-C, and adiponectin levels were measured. Current smoking and alcohol intake habits were evaluated with a questionnaire. All of the parameters were compared between 2 groups displaying frequently observed genotypes: one group consisting of patients having either the R/R or R/X genotype and a second group with the X/X genotype. The frequency of the X allele was 0.55 and the distribution of the genotypes was 35.5% (n = 27) for X/X, 39.5% (n = 30) for R/X, and 25.0% (n = 19) for R/R. Serum HDL-C and adiponectin levels were significantly higher in X/X genotype compared to the R/R or R/X genotype (HDL-C 1.6 ± 0.3 [SD] vs. 1.4 ± 0.2 mmol/L; P<.01, adiponectin 8.8 ± 2.6 vs. 6.9 ± 2.3 μg/mL; P<.01), even after adjustments for confounders (P<.01). There may be a relationship between the ACTN3 genotype and HDL-C and adiponectin levels in rugby players. This may be useful information when determining the individual responses of antiatherogenic markers to exercise. ACTN3 = α-actinin-3 BMI = body mass index CVD = cardiovascular disease HDL-C = high-density lipoprotein cholesterol LDL-C = low-density lipoprotein cholesterol R = arginine (R) at amino acid position 577 of the ACTN3 protein TC = total cholesterol TG = triglyceride X = truncation at amino acid position 577 of the ACTN3 protein.

Interaction of ACTN3 gene polymorphism and muscle imbalance effects on kinematic efficiency in combat sports athletes

[Purpose]The purpose of this study was to determine the interaction of ACTN3 gene polymorphism and muscle imbalance effects on kinematic efficiency changes in combat sports athletes.[Methods]Six types of combat sports athletes (Judo, Taekwondo, boxing, kendo, wrestling, and Korean Ssi-reum) participated in the study. ATCN3 gene polymorphism and muscle imbalance in lower extremity were evaluated followed by analysis of differences of moment in hip, knee, and ankle joint during V-cut jumping and stop. To examine the moment difference due to an interaction of ATCN3 polymorphism and muscle imbalance, all participants were divided into 4 groups (R+MB, R+MIB, X+MB, and X+MIB).[Results]There was no significant difference of hip, knee, and ankle joint moment in R allele and X allele during V-cut jumping and stop based on ACTN3 gene polymorphism. Otherwise, muscle imbalance of knee moment in X-axis and ground reaction force of knee in Z-axis showed a higher significance in muscle imbalance during V-cut jumping and stop compared to muscle balance (p<0.05). In addition, joint analysis showed that muscle imbalance in X allele group had significantly higher knee moment of V-cut ground reaction force in X-axis and higher ankle moment of jumping ground reaction force in X and Z-axis compared to muscle balance with R and/or X group (p <0.05).[Conclusion]This study confirmed that muscle imbalance in lower extremity of combat athletes might induce higher risk factors of sports injury incidence than genetic factor and training might reduce the ratio of sports injury risk incidence.