Elimination of Influences of the ACTN3 R577X Variant on Oxygen Uptake by Endurance Training in Healthy Individuals

Silva, Michelle S.M.; Bolani, Wladimir; Alves, Cléber R.; Biagi, Diogo; Lemos, José R.; Silva, Jeferson L. da; Oliveira, Pedro; Alves, Guilherme B.; Oliveira, Edilamar Menezes de; Negräo, Carlos Eduardo; Dias, Rodrigo Gonçalves; Pereira, Alexandre C.

doi:10.1123/ijspp.2014-0205

Cited by 24 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Whereas the ACTN3 R577X polymorphism has been associated with muscle performance phenotypes in elite and amateur power athletes, studies linking it to cardiometabolic fitness are challenged by a lack of mechanistic evidence [ 5 ]. Herein we identified significant associations between the ACTN3 ancestral R allele and cardiometabolic fitness in a population of healthy young adults.…”

Section: Discussionmentioning

confidence: 99%

“…Previous attempts to identify associations between ACTN3 genotype and cardiovascular fitness tended to be ambiguous in their description of their treadmill protocol, or utilized increases in running speed to change workload [ 5 ]. As such, one interpretation of our results is that the genotype effects on VO 2 peak are unmasked by our use of the Bruce treadmill protocol, a widely used clinical test for maximal oxygen consumption that utilizes a rapidly graded incline to increase the workload [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Uniquely, α-actinin-3 expression is completely absent in 18–20% of the global population because of a common nonsense polymorphism in the ACTN3 gene wherein arginine (R) is converted into a stop codon (X) at residue 577 [ 3 ]. While the frequency of the ACTN3 577X null allele varies significantly between populations, at least one copy of the ACTN3 R577 allele is beneficial for participation in sprint and power sports [ 4 ] whereas the ACTN3 577XX genotype is overrepresented in some endurance athlete cohorts [ 5 ] [ 6 ]. While numerous studies have confirmed associations between the ACTN3 R577 allele and muscle power phenotypes in humans (i.e sprint time, fiber type) there have been far fewer studies linking the ACTN3 577X allele with endurance phenotypes [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…While the frequency of the ACTN3 577X null allele varies significantly between populations, at least one copy of the ACTN3 R577 allele is beneficial for participation in sprint and power sports [ 4 ] whereas the ACTN3 577XX genotype is overrepresented in some endurance athlete cohorts [ 5 ] [ 6 ]. While numerous studies have confirmed associations between the ACTN3 R577 allele and muscle power phenotypes in humans (i.e sprint time, fiber type) there have been far fewer studies linking the ACTN3 577X allele with endurance phenotypes [ 5 ]. Notwithstanding these observations ACTN3 knockout mice exhibit increased recovery from exercise fatigue and a shift towards slow twitch or endurance type skeletal muscle metabolism [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults

et al. 2015

View full text Add to dashboard Cite

Homozygosity for a premature stop codon (X) in the ACTN3 “sprinter” gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) study. Both males and females with the RR vs XX genotype achieved higher mean VO2 peak scores (47.8 ± 1.5 vs 43.2 ±1.8 ml/O2/min, p = 0.002) and exhibited higher resting systolic (115 ± 2 vs 105 ± mmHg, p = 0.027) and diastolic (69 ± 3 vs 59 ± 3 mmHg, p = 0.005) blood pressure suggesting a role for ACTN3 in the maintenance of vascular tone. We subsequently identified the expression of alpha-actinin 3 protein in pulmonary artery smooth muscle, which may explain the genotype-specific differences in cardiovascular adaptation to acute exercise. In addition, we utilized targeted serum metabolomics to distinguish between RR and XX genotypes, suggesting an additional role for the ACTN3 R577X polymorphism in human metabolism. Taken together, these results identify significant cardiometabolic effects associated with possessing one or more functional copies of the ACTN3 gene.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Following a structured literature search, we found five studies that examined the influence of ACTN3 on exercise adaptation to a standardized training programme (Table 1 ). Four of these studied resistance training (Clarkson et al, 2005a ; Delmonico et al, 2007 ; Pereira et al, 2013 ; Erskine et al, 2014 ), and one focused on aerobic training (Silva et al, 2015 ). An additional study (Mägi et al, 2016 ), monitored changes in VO 2peak over a five-year period in elite skiers, with no significant ACTN3 genotype differences.…”

Section: Actn3 As a Modulator Of Training Responsementioning

confidence: 99%

ACTN3: More than Just a Gene for Speed

2017

View full text Add to dashboard Cite

Over the last couple of decades, research has focused on attempting to understand the genetic influence on sports performance. This has led to the identification of a number of candidate genes which may help differentiate between elite and non-elite athletes. One of the most promising genes in that regard is ACTN3, which has commonly been referred to as “a gene for speed”. Recent research has examined the influence of this gene on other performance phenotypes, including exercise adaptation, exercise recovery, and sporting injury risk. In this review, we identified 19 studies exploring these phenotypes. Whilst there was large variation in the results of these studies, as well as extremely heterogeneous cohorts, there is overall a tentative consensus that ACTN3 genotype can impact the phenotypes of interest. In particular, the R allele of a common polymorphism (R577X) is associated with enhanced improvements in strength, protection from eccentric training-induced muscle damage, and sports injury. This illustrates that ACTN3 is more than just a gene for speed, with potentially wide-ranging influence on muscle function, knowledge of which may aid in the future personalization of exercise training programmes.

show abstract

More than a ‘speed gene’: ACTN3 R577X genotype, trainability, muscle damage, and the risk for injuries

et al. 2018

View full text Add to dashboard Cite

A common null polymorphism (rs1815739; R577X) in the gene that codes for α-actinin-3 (ACTN3) has been related to different aspects of exercise performance. Individuals who are homozygous for the X allele are unable to express the α-actinin-3 protein in the muscle as opposed to those with the RX or RR genotype. α-actinin-3 deficiency in the muscle does not result in any disease. However, the different ACTN3 genotypes can modify the functioning of skeletal muscle during exercise through structural, metabolic or signalling changes, as shown in both humans and in the mouse model. Specifically, the ACTN3 RR genotype might favour the ability to generate powerful and forceful muscle contractions. Leading to an overall advantage of the RR genotype for enhanced performance in some speed and power-oriented sports. In addition, RR genotype might also favour the ability to withstand exercise-induced muscle damage, while the beneficial influence of the XX genotype on aerobic exercise performance

show abstract

Elimination of Influences of the ACTN3 R577X Variant on Oxygen Uptake by Endurance Training in Healthy Individuals

Cited by 24 publications

References 0 publications

The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults

The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults

ACTN3: More than Just a Gene for Speed

More than a ‘speed gene’: ACTN3 R577X genotype, trainability, muscle damage, and the risk for injuries

Contact Info

Product

Resources

About