Genes for Elite Power and Sprint Performance: ACTN3 Leads the Way

Nir Eynon, Erik D. Hanson, Alejandro Lucia, Peter J. Houweling, Fleur Garton, Kathryn N. North, David J. Bishop

The ability of skeletal muscles to produce force at a high velocity, which is crucial for success in power and sprint performance, is strongly influenced by genetics and without the appropriate genetic make-up, an individual reduces his/her chances of becoming an exceptional power or sprinter athlete. Several genetic variants (i.e. polymorphisms) have been associated with elite power and sprint performance in the last few years and the current paradigm is that elite performance is a polygenic trait, with minor contributions of each variant to the unique athletic phenotype. The purpose of this review is to summarize the specific knowledge in the field of genetics and elite power performance, and to provide some future directions for research in this field. Of the polymorphisms associated with elite power and sprint performance, the α-actinin-3 R577X polymorphism provides the most consistent results. ACTN3 is the only gene that shows a genotype and performance association across multiple cohorts of elite power athletes, and this association is strongly supported by mechanistic data from an Actn3 knockout mouse model. The angiotensin-1 converting enzyme insertion/deletion polymorphism (ACE I/D, registered single nucleotide polymorphism [rs]4646994), angiotensinogen (AGT Met235Thr rs699), skeletal adenosine monophosphate deaminase (AMPD1) Gln(Q)12Ter(X) [also termed C34T, rs17602729], interleukin-6 (IL-6 -174 G/C, rs1800795), endothelial nitric oxide synthase 3 (NOS3 -786 T/C, rs2070744; and Glu298Asp, rs1799983), peroxisome proliferator-activated receptor-α (PPARA Intron 7 G/C, rs4253778), and mitochondrial uncoupling protein 2 (UCP2 Ala55Val, rs660339) polymorphisms have also been associated with elite power performance, but the findings are less consistent. In general, research into the genetics of athletic performance is limited by a small sample size in individual studies and the heterogeneity of study samples, often including athletes from multiple-difference sporting disciplines. In the future, large, homogeneous, strictly defined elite power athlete cohorts need to be established though multinational collaboration, so that meaningful genome-wide association studies can be performed. Such an approach would provide unbiased identification of potential genes that influence elite athletic performance.