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.

ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study.

BACKGROUND: To date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without quantitative measures of performance. AIM: To examine the association between these variants and sprint time in elite athletes. METHODS: We collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3 R577X and ACE ID variants. RESULTS: On average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec, p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012 London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003). Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance, respectively. CONCLUSIONS: Despite sprint performance relying on many gene variants and environment, the % sprint time variance explained by ACE and ACTN3 is substantial at the elite level and might be the difference between a world record and only making the final.

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

Muscle fibre type is a heritable trait and can partly predict athletic success. It has been proposed that polymorphisms of genes involved in the regulation of muscle fibre characteristics may predispose the muscle precursor cells of a given individual to be predominantly fast or slow. In the present study, we examined the association between 15 candidate gene polymorphisms and muscle fibre type composition of the vastus lateralis muscle in 55 physically active, healthy men. We found that rs11091046 C allele carriers of the angiotensin II type 2 receptor gene (AGTR2; involved in skeletal muscle development, metabolism and circulatory homeostasis) had a significantly higher percentage of slow-twitch fibres than A allele carriers [54.2 (11.1) versus 45.2 (10.2)%; P = 0.003]. These data indicate that 15.2% of the variation in muscle fibre composition of the vastus lateralis muscle can be explained by the AGTR2 genotype. Next, we investigated the frequencies of the AGTR2 alleles in 2178 Caucasian athletes and 1220 control subjects. The frequency of the AGTR2 C allele was significantly higher in male and female endurance athletes compared with power athletes (males, 62.7 versus 51.7%, P = 0.0038; females, 56.6 versus 48.1%, P = 0.0169) and control subjects (males, 62.7 versus 51.0%, P = 0.0006; elite female athletes, 65.1 versus 55.2%, P = 0.0488). Furthermore, the frequency of the AGTR2 A allele was significantly over-represented in female power athletes (51.9%) in comparison to control subjects (44.8%, P = 0.0069). We also found that relative maximal oxygen consumption was significantly greater in male endurance athletes with the AGTR2 C allele compared with AGTR2 A allele carriers [n = 28; 62.3 (4.4) versus 57.4 (6.0) ml min(-1) kg(-1); P = 0.0197]. Taken together, these results demonstrate that the AGTR2 gene C allele is associated with an increased proportion of slow-twitch muscle fibres, endurance athlete status and aerobic performance, while the A allele is associated with a higher percentage of fast-twitch fibres and power-oriented disciplines.

The polygenic profile of Russian football players.

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.

The association of ACE, ACTN3 and PPARA gene variants with strength phenotypes in middle school-age children.

The aim of the study was to determine the association between ACE I/D, ACTN3 R577X and PPARA intron 7 G/C gene polymorphisms and strength-related traits in 457 middle school-age children (219 boys and 238 girls; aged 11 ± 0.4 years). The assessment of different phenotypes was conducted with a number of performance tests. Gene polymorphisms were determined by PCR. The ACE D allele was associated with high results of standing long-jump test in boys [II 148.3 (16.3) cm, ID 152.6 (19.6) cm, DD 158.2 (19.1) cm; P = 0.037]. The ACTN3 R allele was associated with high results of performance tests in males only in combination with other genes (standing long-jump test: P = 0.021; handgrip strength test: P < 0.0001). Furthermore, the male carriers of the PPARA gene C allele demonstrated the best results of handgrip strength testing than GG homozygotes [GG 14.6 (4.0) kg, GC/CC 15.7 (4.3) kg; P = 0.048]. Thus, the ACE, ACTN3 and PPARA gene variants are associated with strength-related traits in physically active middle school-age boys.

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)%; = 0.215; P = 0.049) in the overall muscle biopsy group, and with PRD of all athletes ( = 0.24, P = 0.010), indicating thatACTN3 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.

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

The alpha-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 alpha-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 alpha-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.