ACTN3R577X Polymorphism and Israeli Top-level Athletes

Abstract

A common genetic variation in the alpha-actinin-3 ( ACTN3) gene causes a replacement of an arginine (R) with a premature stop codon (X) at amino-acid 577 (rs1815739). While the R allele has been found to be associated with power-oriented performance, the XX genotype may be linked with endurance ability. To test this hypothesis, we studied the distribution of ACTN3 genotypes in 155 Israeli athletes (age=35.9+12.2 years) classified by sport (endurance runners and sprinters) and in 240 sedentary individuals. The sprinters' allele frequencies (AF: R/X=0.7/0.3) and 577RR genotype distribution percentage (GD: RR=52%) differed markedly from those of the endurance athletes (AF: R/X=0.53/0.47, p=0.000007; GD: RR=18%, p=0.00009) and the control group (AF: R/X=0.55/0.45, p=0.0002; GD: RR=27.3%, p=0.000003). A comparison between the top-level and national-level sprinters revealed that the R allele occurs more often in the top-level sprinters. A significantly higher proportion of the XX genotype was observed in endurance athletes (34%) compared with controls (18%, p=0.02) and sprinters (13%, p=0.002). However, top-level and national level endurance athletes had similar allele and genotype frequencies. We conclude that the ACTN3 R allele is associated with top-level sprint performance and the X allele and XX genotypes may not be critical but rather additive to endurance performance.

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.…”

“…Previous studies from our laboratory indicated that the R577X substitution in the ACTN3 gene (Eynon et al 2009e) and several variants in the PPARGC1A-NRF-TFAM pathway (Eynon et al 2009a;2009b;2009c;2009d;) are associated with elite athletic status. We also suggested that in general, endurance athletes have a polygenic profile that is more adjusted for mitochondrial biogenesis, as opposed to power athletes or non-athletic controls (Eynon et al 2010).…”

“…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.…”

“…Genotype analyses were performed using the polymerase chain reaction (PCR) following restriction fragment length polymorphism (RFLP) analysis as previously described (Eynon et al 2009a;2009b;2009c;2009d;2009e ).…”

“…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). …”