ACTN3 in West vs. East African Athletes

It's nice to see negative results like this one published. Some studies have found associations between this ACTN3 allele and endurance vs. sprint performance (here), but only Europeans have been looked at so far (although I thought they did a study on Kenyans before). We also know that the "endurance" version of this allele (X) is at a higher frequency outside of Africa (here). In this study they look for an association between West African controls vs. "sprint" athletes and Kenyan and Ethiopian controls vs. endurance athletes.

the discussion is short and sweet, and they offer some alternative scenarios (abstract is further below):

The X allele has been observed in all human populations tested so far. The lowest X allele frequencies occur in Kenyan, Nigerian and South African populations (8-11%), resulting in approximately 1% XX genotype frequency. Australian Caucasian and Spanish with European origin, Japanese in northeast Asia, and Javanese in southeast Asia have the highest frequencies of the X allele (44-54%), resulting in XX genotype frequencies from 18 to 25%. The X allele frequencies in the Japanese and Javanese populations are higher than 50%. Papua New Guinea highlanders and Aboriginal Australians display intermediate X allele frequencies (29-36%), resulting in XX genotype frequencies of 10-15% (11).

This study does not support the hypothesis that the ACTN3 null X allele contributes to the success of the East African endurance runners relative to their source populations. In addition, the extremely low XX genotype frequency in the Nigerian control population (0% in this study) rules out the possibility of detecting a lower frequency of the XX genotype in Nigerian power athletes.

There are several possible explanations for the discrepancy between these results and previously published associations seen in athletes of European descent. The low baseline allele frequency of 577X in the three surveyed African populations reduces the effective power of our study, potentially obscuring any genetic association with performance. Alternately, it is possible that the effect of ACTN3 genotype on muscle performance is dependent on other genetic influences, or on environmental variables, that differ between African and non-African populations. For example, many East Africans are subject to environmental influences, such as living and training at altitude and high levels of incidental running during childhood, which play major roles in shaping athletes from this region (12,15) and differ substantially from the childhood experiences of most potential non-African athletes. Such factors may reduce the impact of [alpha]-actinin-3 deficiency on the muscle performance of African individuals.

In conclusion, the results of this study extend our knowledge of the distribution of the 577X null allele of the ACTN3 gene to three previously unexamined African populations. We have shown that the frequency of the 577X allele is substantially lower in Kenyan and Nigerian populations than in any non-African population sampled to date, and it is similar to that seen previously in a South African Bantu-speaking cohort (Table 1) (7). The 577X allele frequency seen in the Ethiopian group is substantially higher, probably reflecting population admixture with non-African groups. We have found no evidence for an association between the R577X polymorphism and endurance performance in East African athletes. The absence of 577XX ([alpha]-actinin-3 deficiency) in controls and athletes from Nigeria would mask any association between the presence of [alpha]-actinin-3 and sprint/power performance. Our data suggest that [alpha]-actinin-3 deficiency is not a major influence on performance in African athletes.

The ACTN3 R577X Polymorphism in East and West African Athletes

YANG, NAN; MACARTHUR, DANIEL G.; WOLDE, BEZABHE; ONYWERA, VINCENT O.; BOIT, MICHAEL K.; LAU, SAU YIN MARY-ANN; WILSON, RICHARD H.; SCOTT, ROBERT A.; PITSILADIS, YANNIS P.; NORTH, KATHRYN

Medicine & Science in Sports & Exercise. 39(11):1985-1988, November 2007.

Purpose: To determine the frequency of the ACTN3 R577X polymorphism (functional R allele and nonfunctional X allele) in a variety of African populations and to examine its influence on the success of elite East African endurance runners and West African sprinters.

Methods: The R577X polymorphism was genotyped in 198 Ethiopian controls and 76 elite Ethiopian endurance athletes, 158 Kenyan controls and 284 elite Kenyan endurance runners, and 60 Nigerian controls and 62 elite Nigerian power athletes. Statistical analyses were performed by exact tests of population differentiation, using Arlequin, version 3. Analyses were carried out using 1 × 10⁶ Markov chain steps, and 1 × 10⁵ dememorization steps.

Results: The frequency of the X allele was extremely low among Kenyans and Nigerians (~1% homozygosity) and higher in Ethiopians (~11% homozygosity). The low baseline frequencies of the three populations tested mean that any associations with sprint performance would likely be obscured. In Ethiopians, where baseline levels of 577XX were about 11%, there was no increased frequency in the endurance athletes.

Conclusion: Our data suggest that [alpha]-actinin-3 deficiency is not a major influence on performance in African athletes.

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