D. V. Popov

The ACTN3 R577X polymorphism in Russian endurance athletes

Objective The functional 577R allele of the α-actinin-3 (ACTN3) gene has been reported to be associated with elite power athlete status, while the nonfunctional 577XX genotype (predicts an α-actinin-3 deficient phenotype) has been hypothesised as providing some sort of advantage for endurance athletes. In the present study, the distribution of ACTN3 genotypes and alleles in Russian endurance-oriented athletes were examined and association between ACTN3 genotypes and the competition results of rowers were sought. Methods 456 Russian endurance-oriented athletes of regional or national competitive standard were involved in the study. ACTN3 genotype and allele frequencies were compared with 1211 controls. The data from the Russian Cup Rowing Tournament were used to search for possible association between the ACTN3 genotype and the long-distance (∼6 km) rowing results of 54 athletes. DNA was extracted from mouthwash samples. Genotyping for the R577X variant was performed by PCR and restriction enzyme digestion. Results The frequencies of the ACTN3 577XX genotype (5.7% vs 14.5%; p<0.0001) and 577X allele (33.2% vs 39.0%; p = 0.0025) were significantly lower in endurance-oriented athletes compared with the controls, and none of the highly elite athletes had the 577XX genotype. Furthermore, male rowers with ACTN3 577RR genotype showed better results (1339 (11) s) in long-distance rowing than carriers of 577RX (1386 (12) s) or 577XX (1402 (10) s) genotypes (p = 0.016). Conclusion Our data show that the ACTN3 577X allele is under-represented in Russian endurance athletes and is associated with the rowers’ competition results.

PPARα gene variation and physical performance in Russian athletes

Peroxisome proliferator-activated receptor α (PPARα) regulates genes responsible for skeletal and heart muscle fatty acid oxidation. Previous studies have shown that the PPARα intron 7 G/C polymorphism was associated with left ventricular growth in response to exercise. We speculated that GG homozygotes should be more prevalent within a group of endurance-oriented athletes, have normal fatty acid metabolism, and increased percentages of slow-twitch fibers. We have tested this hypothesis in the study of a mixed cohort of 786 Russian athletes in 13 different sporting disciplines prospectively stratified by performance (endurance-oriented athletes, power-oriented athletes and athletes with mixed endurance/power activity). PPARα intron 7 genotype and allele frequencies were compared to 1,242 controls. We found an increasing linear trend of C allele with increasing anaerobic component of physical performance (P=0.029). GG genotype frequencies in endurance-oriented and power-oriented athletes were 80.3 and 50.6%, respectively, and were significantly (P<0.0001) different compared to controls (70.0%). To examine the association between PPARα gene variant and fiber type composition, muscle biopsies from m. vastus lateralis were obtained and analyzed in 40 young men. GG homozygotes (n=25) had significantly (P=0.003) higher percentages of slow-twitch fibers (55.5±2.0 vs 38.5±2.3%) than CC homozygotes (n=4). In conclusion, PPARα intron 7 G/C polymorphism was associated with physical performance in Russian athletes, and this may be explained, in part, by the association between PPARα genotype and muscle fiber type composition.

The dependence of preferred competitive racing distance on muscle fibre type composition and ACTN3 genotype in speed skaters

It is generally accepted that muscle fibre composition may influence physical performance. The α‐actinin‐3 (ACTN3) gene R577X polymorphism is suspected to be one of the contributing gene variations in the determination of muscle fibre type composition and athletic status. In the present study, we examined the dependence of average preferred racing distance (PRD) on muscle fibre type composition of the vastus lateralis muscle in 34 subelite Russian speed skaters (20 men and 14 women) who competed in races of different length (500–10,000 m). We also investigated the association between the ACTN3 polymorphism and muscle fibre characteristics in 94 subjects (60 physically active healthy men and 34 speed skaters), as well as the relationship between PRD and ACTN3 genotype in 115 subelite and elite speed skaters. In addition, ACTN3 genotype and allele frequencies of the 115 speed skaters were compared with 1301 control subjects. The ACTN3 XX genotype frequency was significantly lower in sprinters (n = 39) compared with control subjects (2.6 versus 14.5%; P = 0.034). We observed a positive relationship between PRD and the proportion of slow‐twitch muscle fibres that was close to linear, but better fitted a logarithmic curve (r = 0.593, P < 0.0005). The ACTN3 R577X polymorphism was associated with muscle fibre composition (slow‐twitch fibres: RR genotype, 51.7 (12.8)%; RX, 57.4 (13.2)%; XX 61.5 (16.3)%; ρ= 0.215; P = 0.049) in the overall muscle biopsy group, and with PRD of all athletes (ρ= 0.24, P = 0.010), indicating that ACTN3 XX genotype carriers exhibit a higher proportion of slow‐twitch fibres and prefer to skate long‐distance races. However, the majority of the association between muscle fibre type and PRD was independent of ACTN3 genotype. In conclusion, the ACTN3 R577X polymorphism is associated with preferred racing distance in speed skaters and muscle fibre type composition. Thus, it is probably partly via associations with fibre type that the R577X polymorphism contributes to a small but perhaps important component of the ability to perform at a high level in speed skating.

[Hormonal adaptation determines the increase in muscle mass and strength during low-intensity strength training without relaxation].

The study was designed to test the hypothesis that, during strength training, a restricted blood supply to the working muscles stimulates the secretion of anabolic hormones and an increase in the muscle mass and strength can be achieved with significantly lower training loads. During eight weeks, three times a week, 18 young, physically active males trained their leg extensor muscles. Nine subjects (group I) worked at 80% of the maximal voluntary contraction (MVC), whereas the rest (group II) performed their exercise without relaxation and at a lower load (50% MVC). The total training load in group II was significantly lower than in group I (77 ± 5 vs. 157 ± 7 kJ, respectively). The eight-week training of both groups significantly increased the mean maximum strength (by 35 and 21% in groups I and II, respectively) and volume (by 17 and 9%, respectively) of the muscles trained (however, the differences between the groups with respect to these changes were nonsignificant). Group I displayed a higher increase in the blood level of creatine phosphokinase than group II, while group II showed a greater increase in the blood concentration of lactate. In contrast to group I, group II displayed a significant increase in the blood concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), and cortisol. Hence, the suggestion that the secretion of metabolic hormones is triggered by a metabolic, rather than mechanical, stimulus from working muscles seems plausible.

The use of molecular genetic methods for prognosis of aerobic and anaerobic performance in athletes

The distribution of genotypes and alleles of ACE (I/D polymorphism), ACTN3 (R577X), NOS3 (5/4), UCP2 (Ala55Val), and UCP3 (-55C/T) genes, as well as the correlation between the genotype and physiological parameters, was studied in rowers (n = 230) and in a control group (n = 855). The genotypes were determined by analyzing restriction fragment length polymorphism. Physiological parameters were determined with a PM 3 rowing ergometer and a MetaMax 3B gas analyzer. The frequency of the ACE II genotype was significantly higher in elite rowers (n = 107) than in the control subjects. The frequency of the ACTN3 XX genotype, unfavorable for development of speed and strength qualities, was twofold lower in all rowers than in the control subjects. The frequencies of the ACE I, ACTN3 R, UCP2 Val, and UCP3 T alleles increased in the athletes along with an increase in skill, which suggested natural sports selection. In addition, ACE I, NOS3 5, UCP2 Val, and UCP3 T alleles correlated with a high aerobic performance. Thus, the ACE I, NOS3 5, UCP2 Val, and UCP3 T alleles may be regarded as genetic markers associated with enhanced aerobic performance and may be included in a diagnostic system for prognosis of human physical performance.

A common polymorphism of the MCT1 gene and athletic performance.

PURPOSE In red skeletal muscle, monocarboxylate transporter 1 (MCT1) is required for lactate to enter the myocytes for oxidation. The A1470T polymorphism (rs1049434) in the MCT1 gene was shown to be associated with lactate transport rates in human skeletal muscles. The aim of the study was to compare genotype and allele frequencies of the MCT1 gene polymorphism in 323 Russian athletes and 467 nonathletic controls and to investigate the association of the MCT1 gene A1470T polymorphism with maximal oxygen consumption and maximal lactate concentration in rowers (n = 79). METHODS Genotyping for the A1470T MCT1 polymorphism was performed by PCR-RFLP method. Physiological measurements of 79 Russian rowers of national competitive standard were determined during an incremental test to exhaustion on a rowing ergometer. RESULTS Frequencies of the A allele (71.8% vs 62.5%, P < .0001) and AA genotype (59.8% vs 39.4%, P < .0001) were significantly higher in endurance-oriented athletes (n = 142) than in the control group. Mean blood lactate concentration was higher in male rowers with the T allele (AT+TT 10.26 ± 1.89 mmol/L, AA 8.75 ± 1.69 mmol/L, P = .005). CONCLUSIONS MCT1 gene A1470T polymorphism is associated with endurance athlete status and blood lactate level after intensive exercise.

INFLUENCE OF RESISTANCE EXERCISE INTENSITY AND METABOLIC STRESS ON ANABOLIC SIGNALING AND EXPRESSION OF MYOGENIC GENES IN SKELETAL MUSCLE

Introduction: We investigated the effect of resistance exercise intensity and exercise‐induced metabolic stress on the activation of anabolic signaling and expression of myogenic genes in skeletal muscle. Methods: Ten strength‐trained athletes performed high‐intensity [HI, 74% of 1‐repetition maximum (RM)], middle‐intensity (MI, 54% 1RM), or middle‐intensity (54% 1RM) no‐relaxation exercise (MIR). Kinase phosphorylation level and myogenic gene expression in muscle samples were evaluated before, 45 min, 5 h, and 20 h after exercise. Results: The lactate concentration in MI was approximately 2‐fold lower than in the 2 other sessions, and was highest in MIR. The phosphorylation level of extracellular kinase 1/2Thr202/Tyr204 after exercise was related to metabolic stress. Metabolic stress induced a decrease in myostatin mRNA expression, whereas mechano‐growth factor mRNA level depended on exercise intensity. Conclusions: This study demonstrates that both intensity and exercise‐induced metabolic stress can be manipulated to affect muscle anabolic signaling. Muscle Nerve 51: 434–442, 2015

Polymorphism of the vascular endothelial growth factor gene (VEGF) and aerobic performance in athletes

The subject of this study is the frequency distribution of alleles of the vascular endothelial growth factor gene (VEGF; the G-634C polymorphism) in athletes (n = 670) and in a control group (n = 1073) and the relationships of genotypes with aerobic performance in rowers (n = 90). Genetic typing was performed using the analysis of restriction fragment length polymorphism. The frequency of the VEGF C allele in the group of endurance athletes (n = 294) was significantly higher than in the control group and increased together with increasing sports qualification. In addition, a correlation of the VEGF C allele with a high aerobic performance of athletes (according to data on the maximal power and maximal oxygen consumption) and with a substantial contribution to the energy supply of aerobic metabolism (according to the values of maximal lactate content) has been found. It is inferred that the G-634C polymorphism of the VEGF gene is associated with physical performance of athletes and plays a key role in sports selection.

Genome-wide association study identifies three novel genetic markers associated with elite endurance performance

To investigate the association between multiple single-nucleotide polymorphisms (SNPs), aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate (V.O2max) in 80 international-level Russian endurance athletes (46 males and 34 females). To validate obtained results, we further performed case-control studies by comparing the frequencies of the most significant SNPs (with P < 10−5-10−8) between 218 endurance athletes and opposite cohorts (192 Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six ‘endurance alleles’ were identified showing discrete associations with V.O2max both in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs7144481, RBFOX1 rs7191721) associated with endurance athlete status. The C allele of the most significant SNP, rs1572312, was associated with high values of V.O2max (males: P = 0.0051; females: P = 0.0005). Furthermore, the frequency of the rs1572312 C allele was significantly higher in elite endurance athletes (95.5%) in comparison with non-elite endurance athletes (89.8%, P = 0.0257), Russian (88.8%, P = 0.007) and European (90.6%, P = 0.0197) controls and power athletes (86.2%, P = 0.0005). The rs1572312 SNP is located on the nuclear factor I A antisense RNA 2 (NFIA-AS2) gene which is supposed to regulate the expression of the NFIA gene (encodes transcription factor involved in activation of erythropoiesis and repression of the granulopoiesis). Our data show that the NFIA-AS2 rs1572312, TSHR rs7144481 and RBFOX1 rs7191721 polymorphisms are associated with aerobic performance and elite endurance athlete status.

Association of mitochondrial transcription factor ( TFAM ) gene polymorphism with physical performance in athletes

The distribution of allele frequencies for the Ser12Thr mitochondrial transcription factor (TFAM) gene polymorphism was studied in athletes (n = 1537) and control subjects (n = 1113) and the relationship between genotypes and aerobic physical performance was estimated in boat racers (n = 90). Genotyping was performed using analysis of restriction fragment length polymorphism (RFLP). Indices of aerobic physical performance such as maximum oxygen consumption (VO2max) and maximum aerobic power (Wmax) were examined in a test with incremental test to exhaustion, which was performed using a rowing ergometer. It was found that the frequency of the TFAM 12Thr allele in the group of endurance-oriented athletes (n =588) was significantly higher than in the control subjects (14.0% vs. 9.1%; p < 0.0001). In the group of endurance-oriented athletes, it increased with the rise of the athletes’ skill level. Moreover, data on Wmax and VO2max were used to reveal the relationship between the TFAM 12Thr allele and the physical performance in athletes. Thus, the Ser12Thr TFAM gene polymorphism is associated with physical performance in athletes.