The ACTN3 gene in elite Greek track and field athletes

The study of genetic influence in the making of an Olympic champion is still in its nascence, but recent work has provided findings regarding the association of the ACTN3 gene on athletic performance. The aim of this study was to examine genetic differences among elite Greek track and field athletes by analysing a mononucleotide polymorphism in exon 15 of the ACTN3 gene. Results showed that ACTN3 genotype and allele frequencies in the top power-oriented athletes were statistically significantly different from those in a representative random sample of the Greek population: the frequency of the RR ACTN3 genotype in power-oriented athletes vs. the general population was 47.94 % vs. 25.97 %. This result was even more prominent for comparison of the subgroup of sprinters to controls. The results suggest an overall strong association between the presence of the RR genotype and elite power performance.     

Citius and longius (faster and longer) with no α‐actinin‐3 in skeletal muscles?

The muscle protein alpha-actinin-3 (ACTN3) is normally thought to be expressed in type II muscle fibres and to be necessary for high-power, high-velocity muscle contractions, such as those typically seen in speed/power athletes. The authors report the case of a Spanish elite long jumper (two times Olympian, personal best of 8.26 m) whose genotype for the ACTN3 gene is 577XX (ACTN3 deficient). These data suggest that there might be notable exceptions to the concept that ACTN3 is the "gene for speed".     

Association between the ACTN3 R577X polymorphism and female endurance athletes in China

The α-actinin 3 ( ACTN3) gene is absent in 18% of healthy white individuals owing to homozygosity for a premature stop codon polymorphism (rs1815739) and is only expressed in the Z line of fast glycolytic muscle fibres. Previous studies have shown highly significant association between ACTN3 genotype and sprint/power performance, while the nonfunctional allele (577X) was believed to provide an advantage for endurance performance. In this study we tested whether XX genotype was over-represented in Chinese endurance athletes compared to the general population. In a study of 250 Chinese endurance athletes of provincial or national competitive standard and 450 controls, we proved that the ACTN3 XX genotype (21.2 vs. 15.8%; P=0.02) and X allele (51.3 vs. 41.1%; P=0.019) were significantly over-represented in female endurance athletes compared to controls, while no genotype-related differences were observed in male endurance athletes. Besides, the frequency of the ACTN3 XX genotype (28.6%) was the highest in a group of highly elite athletes compared with other groups, which supported the hypothesis that the absence of α-actinin-3 provided some sort of advantage for endurance athletes. Our results indicated that ACTN3 R577X polymorphism was associated with endurance performance in female athletes but not male athletes in China.     

ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players

We examined the association of R577X polymorphism (rs1815739) in the α‐actinin‐3 (ACTN3) gene with “explosive” leg muscle power performance in a group of male and female elite volleyball players (n=66, 31 men, 35 women) and in a group of non‐athletic male and female young adults (n=334, 243 men, 91 women). We assessed power performance by means of the vertical squat and counter‐movement jump tests. We also determined whether the genotypic frequencies of the ACTN3 R577X genotypes differed between groups. We did not observe any effect of the ACTN3 R577X polymorphism on study phenotypes in both groups, regardless of gender (all P>0.05). Genotype frequencies were similar between volleyball and control groups (P=0.095). Moreover, we did not find an association between the ACTN3 R577X polymorphism and the likelihood of being an elite volleyball player using the dominant (RR vs RX+XX) and the recessive model (RR+RX vs XX). In summary, these findings suggest that the ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players.     

Association analysis of the ACTN3 R577X polymorphism with passive muscle stiffness and muscle strain injury

Passive muscle stiffness is considered to be a major factor affecting joint flexibility and is thought to relate to the occurrence of muscle strain injury. In skinned muscle fiber experiments, the R577X polymorphism of the α‐actinin‐3 gene (ACTN 3 ) has been associated with passive muscle stiffness. Our primary purpose was to clarify whether the ACTN 3 R577X polymorphism influences passive stiffness of human muscle in vivo. We also examined whether the ACTN 3 R577X polymorphism is associated with the occurrence of hamstring strain injury. Seventy‐six healthy young male subjects were genotyped for the ACTN 3 R577X (rs1815739) polymorphism. Shear modulus (an index of stiffness) of each hamstring muscle (biceps femoris, semitendinosus, and semimembranosus) was assessed using ultrasound shear wave elastography, and history of hamstring strain injury was collected via a questionnaire. The muscle shear moduli of the semitendinosus and semimembranosus were significantly higher in R‐allele (RR  + RX genotype) carriers than in XX genotype carriers, whereas the shear modulus of the biceps femoris did not differ among the ACTN 3 R577X genotypes. Frequency of past hamstring strain injury also did not differ between the 3 genotypes nor between the R‐allele and XX genotype carriers. This study indicates that RR and RX genotypes of the ACTN 3 R577X polymorphism (corresponding to the presence of α‐actinin‐3 in type II muscle fibers) are associated with increased passive muscle stiffness of the human hamstring in vivo. However, this altered mechanical property might not affect the risk of hamstring muscle strain injury.     

ACTN3: A genetic influence on muscle function and athletic performance

A common variant of the ACTN3 gene, R577X, results in complete deficiency of the alpha-actinin-3 protein in the fast skeletal muscle fibers of more than a billion humans worldwide. We review the evidence that this genetic variant is strongly associated with elite athlete status and with normal variation in human muscle strength and sprinting speed.     

Endurance performance: genes or gene combinations?

We assessed the possible association between variants of the genes encoding for the angiotensin-converting enzyme ( ACE) and alpha-actinin-3 ( ACTN3) (both individually and combined) and several endurance phenotypic traits, e.g., peak power output (PPO), ventilatory (VT) and respiratory compensation threshold (RCT), among others, in professional road cyclists and sedentary controls (n = 46 each). We applied an ANCOVA test using the aforementioned phenotype traits as dependent variables, ACE and/or ACTN3 genotype as the fixed (independent) factor and age and body mass as covariates. We only found a significant genotype effect with no concomitant covariate effect for ACTN3, with cyclists who were not alpha-actinin-3 deficient (RR + RX genotypes) having higher PPO and VT values than their XX counterparts (mean [SEM]: 7.4 (0.1) vs. 7.1 (0.1) W/kg, p = 0.035; and 4.5 (0.1) vs. 4.3 (0.1) W/kg, p = 0.029, respectively). Cyclists with an "extreme" ACTN3 and ACE genotype combination, i.e., most strength/power oriented (DD + RR/RX), had higher RCT values than those with the "intermediate" combinations (II + RX/RR, p = 0.036; and DD + XX, p = .0004) but similar to those with the most endurance oriented genotype (II + XX). No significant differences (p > 0.05) were found in controls. In summary, in world-class cyclists, we only found an association between ACTN3 genotypes and VT and PPO, and between ACTN3/ACE genotype combinations and RCT.     

Does complete deficiency of muscle α actinin 3 alter functional capacity in elderly women? A preliminary report

The sarcomeric protein alpha actinin 3 is localised to the Z line of fast fibres, which are responsible for generating forceful muscle contractions at high velocity. However, a substantial proportion of healthy humans are totally deficient in this protein as they are homozygous for a premature stop codon polymorphism (R577X) in the ACTN3 gene. The purpose of this preliminary study was to assess if the presence or absence of alpha actinin 3 influences the deleterious effects of ageing on muscle output and functional capacity.     

ACTN3 genotype and swimming performance in Taiwan

Studies have shown that the 577R allele of α-actinin-3 (ACTN3) is more prevalent in sprint athletes than in the general population or in endurance athletes. We examined the distribution of ACTN3 R577X (rs 1815739) genotypes and alleles in the Taiwanese general population (603) and in elite sprint swimmers who had participated in international/national events (168). Additionally, 50 pre-adolescent (age 11-13 years) male students and 38 adult males who completed 12-weeks of swimming training, were included in the present study. We found that the frequencies of the R allele were significantly higher in female international sprint swimmers (67.6%) than in national sprint swimmers (50.0%) or in the general population (53.7%). The 25-m performance was significantly improved across the genotypes after swimming training among the pre-adolescent males but not among the adult males. In addition, pre-adolescents with the RR genotype had the best performance both before and after training although not statistically significant. In conclusion, the frequencies of ACTN3 577R allele were significantly higher in female international sprint swimmers than among national sprint swimmers or the general population. Furthermore, male pre-adolescents with either the ACTN3 RX or XX genotype showed a greater improvement in 25-meter swimming performance than those with the RR genotype.     

ACTN3 genotype in professional soccer players

The authors studied the frequency distribution of alpha-actinin-3 (ACTN3) R577X genotypes in 60 top-level professional soccer players. The results were compared with those of 52 elite endurance athletes and 123 sedentary controls. The per cent distribution of RR and RX genotypes in soccer players (48.3% and 36.7%) was significantly higher and lower, respectively, than controls (28.5% and 53.7%) and endurance athletes (26.5% and 52%) (p = 0.041). Although there are notable exceptions, elite soccer players tend to have the sprint/power ACTN3 genotype.     

ACTN3 genotyping by real-time PCR in the Italian population and athletes

PURPOSE: Development of two novel sets of primers and probes to detect R577X and Q523R polymorphisms of the alpha-actinin-3 (ACTN3) gene by real-time PCR. We report the allelic frequencies observed in Italian individuals from the general population and athletes. Athletic performance is influenced by training, environmental factors, and genetic predisposition. Actn3 belongs to a family of actin-binding proteins and is supposed to influence sport performance. METHODS: Primer-probe set design and protocol optimization for real-time PCR genotyping of R577X and Q523R polymorphisms. The assay was verified using a traditional PCR-RFLP approach and applied on an Italian population sample (102 male subjects and 42 athletes). RESULTS: Haplotype distribution confirmed the presence of linkage disequilibrium between the polymorphisms, both in the Italian general population and athletes (respectively: chi = 54.4, P < or = 0.001 and chi = 24.5, P < or = 0.001). Within the general population, a large percentage of homozygous subjects (21.6%) was deficient for Actn3. No significant differences were observed in athletes. The concordance between PCR-RFLP and real-time PCR results was 100and 93% for polymorphisms Q523R and R577X, respectively. CONCLUSION: Real-time PCR represents an effective approach for typing ACTN3 alleles. Allelic frequencies in the Italian population are consistent with those seen in other studies on Caucasians.     

The individual and combined influence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training

Alternative measures of muscle size, strength, and power to those used in previous studies could help resolve the controversy surrounding associations between polymorphisms of the angiotensin‐I converting enzyme (ACE) and α‐actinin‐3 (ACTN3) genes and skeletal muscle phenotypes, and the responses to resistance training (RT). To this end, we measured quadriceps femoris muscle volume (V_m), physiological cross‐sectional area (PCSA), maximum isometric force (F_t), specific force (F_t per unit PCSA), maximum isoinertial strength (1‐RM), and maximum power (W_max; n = 40) before and after 9‐week knee extension RT in 51 previously untrained young men, who were genotyped for the ACE I/D and ACTN3 R577X polymorphisms. ACTN3 R‐allele carriers had greater V_m, 1‐RM, and W_max than XX homozygotes at baseline (all P < 0.05), but responses to RT were independent of ACTN3 genotype (all P > 0.05). Muscle phenotypes were independent of ACE genotype before (all P > 0.05) and after RT (all P > 0.01). However, people with the “optimal” ACE+ACTN3 genotype combination had greater baseline 1‐RM and W_max compared to those with the “suboptimal” profile (both P < 0.0125). We show for the first time that the ACTN3 R577X polymorphism is associated with human V_m and (independently and in combination with the ACE I/D polymorphism) influences 1‐RM and W_max.     

ACTN3 genotype in professional endurance cyclists

The Z-disk protein alpha-actinin-3 is only expressed in type II muscle fibres, which are responsible for generating forceful contractions at high velocity. Despite the evolutionary conservation of alpha-actinin-3, approximately one in every five Caucasians of European ancestry is totally deficient in this protein, due to homozygosity for a R577X polymorphism in the ACTN3 gene. This, together with the results of recent research on elite athletes, suggests that the "null" XX polymorphism might confer some advantage to endurance performance events. To test this hypothesis, we studied the frequency distribution of R577X genotypes in a group of 50 top-level male professional cyclists (26.9 +/- 0.4 yrs [mean +/- SEM]; VO2max: 73.5 +/- 0.8 ml x kg (-1) x min (-1)). Their results were compared with those of a group of 52 Olympic-class male endurance runners (26.8 +/- 0.6 yrs; VO2max: 73.3 +/- 0.8 ml x kg (-1) x min (-1)) and 123 healthy, sedentary male controls. All subjects were Caucasian, and of European ancestry. No significant differences (p > 0.05) were found between groups: RR: 28.5 %; RX: 53.6 % and XX: 17.9 % in controls; RR: 28.0 %; RX: 46.0 % and XX: 26.0 % in cyclists; and RR: 25.0 %; RX: 57.7 %; XX: 17.3 % in runners). No differences were found in indices of endurance performance (VO2peak or ventilatory thresholds) between athlete carriers of each R577X genotype. In summary, although the alpha-actinin-3 deficient XX genotype may be detrimental for sprint performance in humans, the R577X polymorphism of the ACTN3 gene does not appear to confer an advantage on the ability of male athletes to sustain extreme endurance performance.     

Is there an association between ACTN3 R577X polymorphism and muscle power phenotypes in young,non‐athletic adults?

We investigated the association between ACTN3 R577X polymorphism and jumping (vertical squat and counter‐movement jump tests) and sprint ability (30 m dash) in non‐athletic, healthy young adults [N=284 (217 male), mean (SD) age: 21 (2) years]. We analyzed the differences in the study phenotypes among ACTN3 R577X genotypes by one‐way analysis of covariance before and after adjusting for sex, age, weight and height (confounders). We also compared the genotype and allele frequencies between those with the best and worst results in the aforementioned tests (≥90th vs <90th of the sex‐specific percentile, respectively). We used logistic regression to calculate the odds ratio (OR) for having the best performance. We did not observe a significant association between ACTN3 R577X genotypes and the study phenotypes before and after adjusting for potential confounders, nor after analyzing males and females separately. We did not observe significant differences in genotype frequencies between those with the best or the worst performance. The OR for an individual with the RR genotype to be in the top 10 percentile was <1.00 for jump tests and <1.015 for sprint tests (all P>0.05). In summary, α‐actinin‐3 deficiency does not negatively influence the ability to generate explosive leg muscle power in a young non‐athletic population.     

World-class performance in lightweight rowing: is it genetically influenced? A comparison with cyclists, runners and non-athletes

In this study, genotype frequencies of several polymorphisms that are candidates to influence sports performance (ie, ACTN3 R577X, ACE ID, PPARGC1A Gly482Ser, AMPD1 C34T, CKMM 985bp/1170bp and GDF8 (myostatin) K153R) were compared in 123 nonathletic controls, 50 professional cyclists, 52 Olympic-class runners and 39 world-class rowers (medallists in world championships, lightweight category). Significant differences in genotype distributions among the groups were not found except for the ACE gene, that is, lower (p<0.05) proportion of II in rowers (10.3%) than in the total subject population (22.3%). In summary, sports performance is likely polygenic with the combined effect of hundreds of genetic variants, one possibly being the ACE ID polymorphism (at least in the sports studied here), but many others remain to be identified.     

ACTN3 genotype in Spanish elite swimmers: No “heterozygous advantage”

The aim of the present case‐control study was to examine the association of the ACTN3 R577X genotype with elite swimming status. We compared a group of Spanish (Caucasian) elite swimmers (n = 88) with other cohorts of the same ethnic origin, i.e., nonathletic controls (n = 343) and other types of athletes who are in both end‐points of the sports performance continuum, i.e., world‐class power (n = 119) and endurance male athletes (n = 154). Swimmers had a lower odds ratio (OR) of having the RX genotype [1.815, 95% confidence intervals (CI): 0.899–3.664] compared with nonathletic controls, yet the association did not reach statistical significance (P = 0.096). Endurance athletes had greater OR of having the XX genotype (OR: 2.88, 95% CI: 1.162–7.135, P = 0.022), or the RX+XX genotype (OR: 1.903, 95% CI: 1.015–3.567, P = 0.045) compared with swimmers. No other association was found. In summary, we did not observe an association between the ACTN3 R577X polymorphism and elite swimmer's status, suggesting that any influence of this polymorphism is not of sufficient magnitude as to significantly influence elite swimming performance, at least in Spanish athletes.     

The genetics of endurance: Frequency of the ACTN3 R577X variant in Ironman World Championship athletes

ObjectivesTo investigate the frequency of the ACTN3 R577X polymorphism in elite endurance triathletes, and whether ACTN3 R577X is significantly associated with performance time.DesignCross-sectional study.MethodsSaliva samples, questionnaires, and performance times were collected for 196 elite endurance athletes who participated in the 2008 Kona Ironman championship triathlon. Athletes were of predominantly North American, European, and Australian origin. A one-way analysis of variance was conducted to compare performance times between genotype groups. Multiple linear regression analysis was performed to model the effect of questionnaire variables and genotype on performance time. Genotype and allele frequencies were compared to results from different populations using the chi-square test.ResultsPerformance time did not significantly differ between genotype groups, and age, sex, and continent of origin were significant predictors of finishing time (age and sex: p < 5 × 10^?6; continent: p = 0.003) though genotype was not. Genotype and allele frequencies obtained (RR 26.5%, RX 50.0%, XX 23.5%, R 51.5%, X 48.5%) were found to be not significantly different from Australian, Spanish, and Italian endurance athletes (p > 0.05), but were significantly different from Kenyan, Ethiopian, and Finnish endurance athletes (p < 0.01).ConclusionsGenotype and allele frequencies agreed with those reported for endurance athletes of similar ethnic origin, supporting previous findings for an association between 577X allele and endurance. However, analysis of performance time suggests that ACTN3 does not alone influence endurance performance, or may have a complex effect on endurance performance due to a speed/endurance trade-off.     

FHIT基因研究进展

FHIT基因是定位于染色体3p14.2区域的候选肿瘤抑制基因,在许多肿瘤,特别是环境致癌物引起的上皮肿瘤中经常发生改变,在辐射引起的癌症中也有改变,参与细胞周期和细胞凋亡的调控,但其作用的机理尚未完全阐明。     

ACE and ACTN3 genotypes in older women: muscular phenotypes

This study examined the association between ACE I/D and ACTN3 R577X polymorphisms and muscle-related phenotypes and their adaptation to resistance training in older women. Volunteers (n=246;age=66.7 ± 5.5 years) underwent quadriceps strength assessment using isokinetics and fat-free mass by dual energy X-ray absorptiometry. 79 volunteers performed 24 weeks of resistance training and 75 were studied as controls. Genotypes were identified by standard procedures. No associations were observed for muscle strength for either gene, but volunteers carrying the D/D genotype presented higher appendicular fat-free mass compared to the I-allele carriers (6.3 ± 0.1 vs. 6.1 ± 0.1 kg/m (2)). The X-allele carriers presented higher relative fat-free mass when compared to homozygous R/R (16.3 ± 0.1 vs. 15.9 ± 0.1 kg/m (2)). All fat-free mass variables were significantly greater for carriers of both X/X and D/D genotypes. In response to RT, only the I-allele carriers significantly increased fat-free mass and a significant training × genotype interaction was noted. These findings do not support a pivotal role for the studied polymorphisms in determining muscle strength in older women, but suggest a modest role in fat-free mass determination. Of note, the results provide a novel insight that these genetic variations may interact to determine muscle mass in older women.