A December 1st article in the New York Times reports that in Boulder, Colorado parents have been given the opportunity to genetically test their children through Atlas Sports Genetics. A $149 test is now available, which aims to “predict a child’s natural athletic strengths.” Atlas states that focusing this testing on children from infancy to about 8 years in age is ideal, because “physical tests to gauge future sports performance at that age are, at best, unreliable.” Research primarily performed at the University of Sydney and published in 2003 regarding the gene ACTN3, prompted this business endeavor. This single gene, of the more than 20,000 in the human genome, is being touted as a reliable predictor for whether a person would be well-suited for speed and power sports versus endurance activities.

Some consider the test a good investment for their children, as it could lead to a college scholarship or career as a professional athlete. However, can testing one gene be enough to determine someone’s particular sports niche or end capabilities? Dr. Theodore Friedmann, director of the University of California – San Diego Medical Center’s interdepartmental gene therapy program disagrees, calling it “an opportunity to sell new versions of snake oil.” He added that “I don’t deny that these genes have a role in athletic success, but it’s not that black and white.”

The director of the functional genomics laboratory at the University of Maryland, Dr. Stephen M. Roth, who has studied ACTN3, stated that “the idea that it will be one or two genes that are contributing to the Michael Phelpses or the Usain Bolts of the world I think is shortsighted, because it’s much more complex than that.” He added that “athletic performance is already known to be affected by more than 200 genes.”

Yang et al. reported in the American Society of Human Genetics that ACTN3 is associated with human elite athletic performance. The specific alleles found at this gene locus code for the presence or absence of α-actinin-3, a protein that is highly specific to fast-twitch type II fibers. For clarification, alleles are the different versions of a gene (for example, one allele may code for brown hair, while another may code for blonde hair). A locus is the location on gene that the alleles influencing a particular trait can be found. The possible genotypes are either 577X, 577RX, or 577R. 577X is a stop codon, a sequence of nucleotides that terminates the production of a specific protein; in other words, it terminates translation. Individuals with this genotype do not produce α-actinin-3 and the absence of a disease state for these individuals is thought to be attributable to compensation by α-actinin-2, a similar protein found in slow-twitch type I fibers. Simply stated, individuals with the 577X genotype readily express the form of the actinin protein more characteristic of slow-oxidative type I muscle fibers. The opposite is true of individuals with the 577R genotype. They readily express the α-actinin-3 protein found in faster-twich type II fibers. 577RX are heterozygotes that will exhibit α-actinin-3 to some extent.

The α-actinins are a family of actin-binding proteins related to dystrophin, a vital structural protein whose absence is the underlying pathology of muscular dystrophy. The α-actinins are components of the Z-line in the sarcomere that crosslink the actin (thin) filaments. They are believed to perform the static function of maintaining an ordered myofibrillar array, coordinating myofibril contractions. The study authors argue that the advantages of this protein lie in three major mechanisms. Sarcomeric α-actinins are associated with glycogen phosphorylase and other glycolytic enzymes which could shift glucose metabolism to the more anaerobic or aerobic pathways. The actinins are also associated with signaling factors that aid in the determination of fiber types. Finally, α-actinin-3 may be evolutionarily optimized for the minimization of damage caused by eccentric contractions. Therefore, their presence or absence may result in the conferral of specific advantages associated with fast-twitch or slower-twitch activities, respectively.

Eighteen percent of healthy white individuals were found to be completely absent of α-actinin-3. Interestingly, 25% of Asian populations were found to be α-actinin-3 deficient, while <1% of the African Bantu population were characterized by the 577X genotype. More significantly, the research scientists analyzed elite sprint/power and endurance athletes as well. The ACTN3 gene of 107 total elite-level (international-competition) athletes, 72 male and 35 female, were determined. Fifty of those athletes had competed in the Olympic games.

The results found that male sprint athletes had a lower frequency of the 577X genotype (lacking α-actinin-3) compared to the non-athletic population, while even more significant was the finding that no female sprint athlete lacked the α-actinin-3 protein altogether. Sprint athletes altogether had a lower frequency of the heterozygous RX genotype (45% vs. 52%) in comparison to controls. Elite endurance athletes had a higher frequency of the 577X gene than controls did (24% vs. 18%). These results led the researchers to conclude that the 577R allele at the ACTN3 gene provides an advantage for power and sprint activities. The fact that it was not as profound in males was believed to be due to the androgenic hormone response to training in males. However, all male Olympian power athletes did have at least one copy of the 577R gene (they were at a minimum heterozygous and did not completely lack α-actinin-3) suggesting that at the most elite levels of competition, “every variable counts.”

The study researchers admitted that at least 73 genetic loci have been associated with fitness and performance phenotypes, suggesting that Dr. Roth’s estimate of 200 may be inflated, although it would be naïve to believe that we have identified them all. This paints the picture that ACTN3 may be a very minor piece of the picture; but a definite piece nonetheless. Now, as to whether this research can justify paying $149 to determine whether this one piece is present and what implications can be drawn about placing a child in football versus soccer is up to parents. More importantly, parents should focus on whether the child gets enough physical activity and derives enjoyment from those activities. The bottom line may be that unless you are attempting to breed an Olympic athlete this information has very limited relevance. Dr. Roth concedes “is it going to affect little Johnny when he participates in soccer, or Suzy’s ability to perform sixth grade track and field?, there’s very little evidence to suggest that.”