ACTN3 Genotype Is Associated with Human Elite Athletic Performance

Abstract

There is increasing evidence for strong genetic influences on athletic performance and for an evolutionary "trade-off" between performance traits for speed and endurance activities. We have recently demonstrated that the skeletal-muscle actin-binding protein alpha-actinin-3 is absent in 18% of healthy white individuals because of homozygosity for a common stop-codon polymorphism in the ACTN3 gene, R577X. alpha-Actinin-3 is specifically expressed in fast-twitch myofibers responsible for generating force at high velocity. The absence of a disease phenotype secondary to alpha-actinin-3 deficiency is likely due to compensation by the homologous protein, alpha-actinin-2. However, the high degree of evolutionary conservation of ACTN3 suggests function(s) independent of ACTN2. Here, we demonstrate highly significant associations between ACTN3 genotype and athletic performance. Both male and female elite sprint athletes have significantly higher frequencies of the 577R allele than do controls. This suggests that the presence of alpha-actinin-3 has a beneficial effect on the function of skeletal muscle in generating forceful contractions at high velocity, and provides an evolutionary advantage because of increased sprint performance. There is also a genotype effect in female sprint and endurance athletes, with higher than expected numbers of 577RX heterozygotes among sprint athletes and lower than expected numbers among endurance athletes. The lack of a similar effect in males suggests that the ACTN3 genotype affects athletic performance differently in males and females. The differential effects in sprint and endurance athletes suggests that the R577X polymorphism may have been maintained in the human population by balancing natural selection.

Genes and the ageing muscle: a review on genetic association studies

“…The α-actinin-3-deficient XX genotype (with a frequency of~18% among European Caucasians) is believed to preclude top-level athletic performance in 'pure' power and sprint sports (e.g. sprinting, jumping events), especially in women (Yang et al 2003). In contrast, compared with the general population, the X allele tends to be overrepresented in those humans with an 'extreme endurance phenotype', i.e.…”

Physiological variables and mitochondrial-related genotypes of an athlete who excels in both short and long-distance running

“…It has been demonstrated that the RR genotype is over-represented in several groups of power-athletes (Druzhevskaya et al 2008;Eynon et al 2009e;Niemi and Majamaa, 2005;Yang et al 2003), with the overall conclusion that this specific genotype may confer an advantage in power-oriented sports events, e.g. sprint, jumping or throwing.…”

“…We genotyped six genetic SNPs in the PPARGC1A-NRF-TFAM pathway genes, which are known to be associated with endurance exercise performance capacity: (Eynon et al 2009d;He et al 2008); (iii) NRF2 C/T (rs8031031) (Eynon et al 2009a); (iv) peroxisome proliferator-activated receptor alpha (PPARA) intron 7 G/C (rs4253778) (Ahmetov et al 2006;Eynon et al 2009b); (v) peroxisome proliferator-activated delta (PPARD) C294T (Eynon et al 2009c); (Skogsberg et al 2003); and (vi) PPARGC1A Gly482Ser (Eynon et al 2009c;Lucia et al 2005). We also studied the ACTN3 R577X polymorphism, which is known to be associated with power-oriented performance (Druzhevskaya et al 2008;Eynon et al 2009e;Niemi and Majamaa, 2005;Yang et al 2003). The studied polymorphisms and genotypes of the Israeli endurance runner are presented in Table 2.…”

“…To date, over 20 single nucleotide polymorphisms (SNPs) have been found to be individually associated with elite athletic status, ranging from endurance to sprint/power-oriented events (Ostrander et al 2009). Among them are muscle-specific SNPs namely; the R577X substitution in the α-actinin-3 (ACTN3) gene (Druzhevskaya et al 2008;Eynon et al 2009e;Niemi and Majamaa, 2005;Yang et al 2003), and the A/G SNP in the muscle-specific creatine kinase (CK-MM Ncol) gene ( Santiago et al 2010). …”

Against Genetic Tests for Athletic Talent: The Primacy of the Phenotype

“…On the 100-meter sprint race, genetic predispositions for developing explosive power and speed are crucial. These are basic bio-motor abilities and can be associated relatively clearly with genetic predispositions (3,18). In this context one could think that genetic tests for identifying talent would be of significant value.…”