Association of the ACTN3 R577X polymorphism with power athlete status in Russians

The α-actinin-3 (ACTN3) gene encodes a Z-disc structural protein which is found only in fast glycolytic muscle fibers. A common nonsense polymorphism in codon 577 of the ACTN3 gene (R577X) results in α-actinin-3 deficiency in XX homozygotes. Previous reports have shown a lower proportion of the ACTN3 XX genotype in power-oriented athletes compared to the general population. In the present study we tested whether XX genotype was under-represented in Russian power-oriented athletes. The study involved 486 Russian power-oriented athletes of regional or national competitive standard. ACTN3 genotype and allele frequencies were compared to 1,197 controls. The frequencies of the ACTN3 XX genotype (6.4 vs. 14.2%; P < 0.0001) and X allele (33.3 vs. 38.7%; P = 0.004) were significantly lower in power-oriented athletes compared to controls. Furthermore, the lowest (3.4%) frequency of the ACTN3 XX genotype was found in a group of highly elite athletes, supporting the hypothesis that the presence of α-actinin-3 has a beneficial effect on the function of skeletal muscle in generating forceful contractions at high velocity. In conclusion, ACTN3 R577X polymorphism was associated with power athlete status in Russians

Epigenetic modifications during exercise

Mapping on the human genome and genome of other organisms revealed not only the DNA organization principles, but also showed the regulation complexity of the structural and metabolic genes expression. It turned out that external influences such as nutrition, stress, physical activity and other external stimuli change genes expression and control it through a complex set of regulatory mechanisms. A complex set of molecular mechanisms, including genetic and epigenetic factors, is involved in the regulation of skeletal muscle metabolism. Epigenetic regulation of gene expression in human skeletal muscles is carried out at three levels: DNA methylation, histone modification and mRNA-microRNA interaction. The article considers the possible mechanisms of epigenetic regulation of intracellular metabolism of skeletal muscles during single and systematic exercises. © 2018 Teoriya i praktika fizicheskoy kul'tury i sporta. All rights reserved

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 longdistance (∼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

The -9/+9 polymorphism of the bradykinin receptor beta 2 Gene and athlete status: A study involving two European cohorts

Previous studies concerning the relevance of BDKRB2 gene polymorphisms revealed that the absence (-9 allele) of a nine-base-pair sequence in exon 1 of the BDKRB2 gene is correlated with higher skeletal muscle metabolic efficiency, glucose uptake during exercise, and endurance athletic performance. The aim of the study was to investigate the association between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of eastern European athletes. We examined the genotype distribution of the BDKRB2 9/+9 polymorphic site in a group of Polish athletes and confirmed the results obtained in a replication study of Russian athletes. Three hundred and two Polish athletes and 684 unrelated sedentary controls, as well as 822 Russian athletes and 507 unrelated sedentary volunteers, were recruited for this study. All samples were genotyped for the -9/+9 polymorphism within exon 1 of the BDKRB2 gene using polymerase chain reaction. Significance was assessed by chi square analysis with Bonferroni's correction for multiple testing. We found no statistical difference in the -9/+9 genotype and allele frequencies in two groups of athletes divided into four subgroups: endurance, sprint-endurance, sprint-strength, and strength athletes, compared with controls. There were no significant differences in allele frequencies (p = 0.477) and genotype distribution (p = 0.278) in the initial and replication studies. Thus, no association was found between the BDKRB2 -9/+9 polymorphism and elite athletic status in two cohorts of eastern European athletes

The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes

Endurance performance is a complex phenotype subject to the influence of both environmental and genetic factors. Although the last decade has seen a variety of specific genetic factors proposed, many in metabolic pathways, each is likely to make a limited contribution to an 'elite' phenotype: it seems more likely that such status depends on the simultaneous presence of multiple such variants. The aim of the study was to investigate individually and in combination the association of common metabolic gene polymorphisms with endurance athlete status, the proportion of slow-twitch muscle fibers and maximal oxygen consumption. A total of 1,423 Russian athletes and 1,132 controls were genotyped for 15 gene polymorphisms, of which most were previously reported to be associated with athlete status or related intermediate phenotypes. Muscle fiber composition of m. vastus lateralis in 45 healthy men was determined by immunohistochemistry. Maximal oxygen consumption of 50 male rowers of national competitive standard was determined during an incremental test to exhaustion on a rowing ergometer. Ten 'endurance alleles' (NFATC4 Gly160, PPARA rs4253778 G, PPARD rs2016520 C, PPARGC1A Gly482, PPARGC1B 203Pro, PPP3R1 promoter 5I, TFAM 12Thr, UCP2 55Val, UCP3 rs1800849 T and VEGFA rs2010963 C) were first identified showing discrete associations with elite endurance athlete status. Next, to assess the combined impact of all 10 gene polymorphisms, all athletes were classified according to the number of 'endurance' alleles they possessed. The proportion of subjects with a high (≥9) number of 'endurance' alleles was greater in the best endurance athletes compared with controls (85.7 vs. 37.8%, P = 7.6 × 10-6). The number of 'endurance' alleles was shown to be positively correlated (r = 0.50; P = 4.0 × 10-4) with the proportion of fatigue-resistant slow-twitch fibers, and with maximal oxygen consumption (r = 0.46; P = 7.0 × 10-4). These data suggest that the likelihood of becoming an elite endurance athlete depends on the carriage of a high number of endurance-related alleles

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. © Springer-Verlag 2006

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

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

Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance.

Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of single nucleotide polymorphisms or the insertion/deletion variants in small, often heterogeneous cohorts (i.e., made up of athletes of quite different sport specialties) have not generated the kind of results that could offer solid opportunities to bridge the gap between basic research in exercise sciences and deliverables in biomedicine. A retrospective view of genetic association studies with complex disease traits indicates that transition to hypothesis-free genome-wide approaches will be more fruitful. In studies of complex disease, it is well recognized that the magnitude of genetic association is often smaller than initially anticipated, and, as such, large sample sizes are required to identify the gene effects robustly. A symposium was held in Athens and on the Greek island of Santorini from 14-17 May 2015 to review the main findings in exercise genetics and genomics and to explore promising trends and possibilities. The symposium also offered a forum for the development of a position stand (the Santorini Declaration). Among the participants, many were involved in ongoing collaborative studies (e.g., ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE). A consensus emerged among participants that it would be advantageous to bring together all current studies and those recently launched into one new large collaborative initiative, which was subsequently named the Athlome Project Consortium