Overcoming the barrier of sample size: The ACTN3 R577X polymorphism across three groups of elite European athletes

N. Eynon,¹ D.J. Bishop,¹ V.P. Pushkarev,² P. Cieszczyk³ and A. Lucia,⁴ ¹School of Sports and Exercise Sciences, and Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, VIC 8001, Australia, ²Ural State University of Physical Culture, Chelyabinsk, Russia, ³Department of Physical Culture and Health Promotion, University of Szczecin, Poland and ⁴Universidad Europea de Madrid, Madrid, Spain.

The ACTN3 R577X common polymorphism was identified by North et al. (1999). We (Eynon et al., 2009), and the Norths group (Yang et al., 2003), have previously observed a significantly lower frequency of ACTN3 577XX (α-actinin-3 null), in elite power athletes (i.e. sprinters, jumpers and throwers) compared to healthy controls. In contrast, elite endurance athletes (i.e. long-distance runners and triathletes) had higher frequencies of the ACTN3 577XX genotype compared to controls (Eynon et al., 2009; Yang et al., 2003) Subsequently, this association has been replicated in several cohorts of elite athletes from different ancestries, with some studies unable to find a significant association with performance possibly due to sample size limitation (Eynon et al., 2011). In fact, most of the aforementioned studies performed with elite athletes were limited by a relatively low sample size (n ≤ 200). In the present study, for the first time, we were able to recruit over 600 elite male athletes from three different European countries in an attempt to overcome this barrier.

Aim: To compare the frequency distribution of the ACTN3 R577X polymorphism between elite endurance athletes, elite sprint/power athletes, and ethnically-matched, non-athletic controls in a large group of European Caucasians, from Spain, Poland and Russia. We also examined the association of the ACTN3 R577X with respect to the performance level (world-class and national level) of both endurance and power athletes.

Methods: A total of 633 athletes (endurance athletes n=278; sprint/power athletes n=355) and 808 controls, from Spain, Poland and Russia, were genotyped for the ACTN3 R577X polymorphism. All participants were unrelated European males and all Caucasians for ≥ 3 generations. We included athletes in the study sample only if they had participated in national/international championships.

Results: The odds ratio (OR) of having the XX genotype vs having the RR genotype (co-dominant effect) for male power athletes was 0.54 (95% confidence interval (CI): 0.34-0.48; P=0.006) compared with sedentary controls. The OR of having the XX genotype vs having the RR (co-dominant effect) for endurance athletes was 1.88 (95% CI: 1.07-3.31; P=0.006) compared with power athletes. The OR of having the XX genotype vs having the recessive trait for endurance world-class athletes was 3.74 (95% CI: 1.08-12.94; P=0.038) compared with endurance national-level athletes.

Conclusion: Our data provide strong support for the potential influential role of the ACTN3 R577X polymorphism to elite athletic status.

Eynon N, Duarte JA, Oliveira J, Sagiv M, Yamin C, Meckel Y, Sagiv M & Goldhammer E (2009). ACTN3 R577X polymorphism and Israeli top-level athletes. International Journal of Sports Medicine 30, 695-698.

Eynon N, Ruiz JR, Oliveira J, Duarte JA, Birk R & Lucia A (2011). Genes and elite athletes: a roadmap for future research. The Journal of Physiology 589, 3063-3070.

North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S & Beggs AH (1999). A common nonsense mutation results in α-actinin-3 deficiency in the general population. Nature Genetics 21, 353-354.

Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S & North K (2003). ACTN3 genotype is associated with human elite athletic performance. American Journal of Human Genetics 73, 627-631.