Irina V. Astratenkova

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.

Association of a PPARD polymorphism with human physical performance

Peroxisome proliferator-activated receptor δ (PPARδ) regulates the expression of genes involved in lipid and carbohydrate metabolism. To examine the association of the functional +294T/C polymorphism of PPARD with human physical performance, the distribution of PPARD alleles and genotypes was studied in a cohort of athletes (N = 1256), stratified by specialization and skill level, and in controls (N = 610). The frequency of PPARD allele C (with a higher transcriptional activity compared to allele T) in the group of endurance-oriented athletes (N = 898) was significantly higher than in controls (18.3% vs. 12.1%, P < 0.0001). Moreover, in the group of endurance-oriented athletes participating in cyclic sports, the frequency of allele C increased with growing skill level. Thus, PPARD allele C was associated with predisposition to endurance performance.

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.

The polygenic profile of Russian football players

Abstract Research concerned with predictors of talent in football has highlighted a number of potentially important and partially inherited measures such as body size, anaerobic power, aerobic capacity, agility, psychological profile, game intelligence and susceptibility to injuries. Genotyping for performance-associated DNA polymorphisms at an early age could be useful in predicting later success in football. The aim of the study was to investigate individually and in combination the association of common gene polymorphisms with football player’s status. A total of 246 Russian football players and 872 controls were genotyped for 8 gene polymorphisms, which were previously reported to be associated with athlete status. Four alleles (ACE D, ACTN3 Arg577, PPARA rs4253778 C and UCP2 55Val) were first identified, showing discrete associations with football player’s status. Next, we determined the total genotype score (TGS, from the accumulated combination of the 4 polymorphisms, with a maximum value of 100 for the theoretically optimal polygenic score) in athletes and controls. The mean TGS was significantly higher in football players (52.0 (17.6) vs. 41.3 (15.5); P < 0.0001) than in controls. These data suggest that the likelihood of becoming a football player depends on the carriage of a high number of “favourable” gene variants.

AGTR2 gene polymorphism is associated with muscle fibre composition, athletic status and aerobic performance

What is the central question of this study? Variations in genes are considered to be molecular determinants maintaining the expression of the slow or fast myosin heavy chains of adult skeletal muscle. The role of polymorphisms of candidate genes involved in skeletal muscle development, energy homeostasis and thyroid and calcium metabolism in the determination of muscle fibre type has not previously been reported. What is the main finding and its importance? We show that the AGTR2 rs11091046 C allele is associated with an increased proportion of slow‐twitch muscle fibres, endurance athlete status and aerobic performance. Such findings have important implications for our understanding of muscle function in both health and disease.

The -9 /+9 Polymorphism of the Bradykinin Receptor Beta 2 Gene and Athlete Status: A Study Involving Two European Cohorts

Abstract 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 Bonferronis 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.

Association analysis of ACE , ACTN3 and PPARGC1A gene polymorphisms in two cohorts of European strength and power athletes

The performance of professional strength and power athletes is influenced, at least partly, by genetic components. The main aim of this study was to investigate individually and in combination the association of ACE (I/D), ACTN3 (R577X) and PPARGC1A (Gly482Ser) gene polymorphisms with strength/power-oriented athletes’ status in two cohorts of European athletes. A cohort of European Caucasians from Russia and Lithuania (161 athletes: by groups – weightlifters (87), powerlifters (60), throwers (14); by elite status – ‘elite’ (104), ‘sub-elite’ (57); and 1,202 controls) were genotyped for ACE, ACTN3 and PPARGC1A polymorphisms. Genotyping was performed by polymerase chain reaction and/or restriction fragment length polymorphism analysis. Statistically significant differences in ACTN3 (R577X) allele/genotype distribution were not observed in the whole cohort of athletes or between analysed groups separately when compared with controls. The odds ratio for athletes compared to controls of the ACE I/I genotype was 1.71 (95% CI 1.01-2.92) in the Russian cohort and for the ACE I/D genotype it was 2.35 (95% CI 1.10-5.06) in the Lithuanian cohort. The odds ratio of being a powerlifter in PPARGC1A Ser/Ser genotype carriers was 2.11 (95% CI: 1.09-4.09, P = 0.026). The ACTN3 (R577X) polymorphism is not associated with strength/power athletic status in two cohorts of European athletes. The ACE I/I genotype is probably the ‘preferable genotype’ for Russian athletes and the ACE I/D genotype for Lithuanian strength/power athletes. We found that the PPARGC1A (Gly482Ser) polymorphism is associated with strength/power athlete status. Specifically, the PPARGC1A Ser/Ser genotype is more favourable for powerlifters compared to controls.