ACTN3 Genotype in Professional Endurance Cyclists

Abstract

The Z-disk protein α-actinin-3 is only expressed in type II muscle fibres, which are responsible for generating forceful contractions at high velocity. Despite the evolutionary conservation of α-actinin-3, approximately one in every five Caucasians of European ancestry is totally deficient in this protein, due to homozygosity for a R577X polymorphism in the ACTN3 gene. This, together with the results of recent research on elite athletes, suggests that the “null” XX polymorphism might confer some advantage to endurance performance events. To test this hypothesis, we studied the frequency distribution of R577X genotypes in a group of 50 top-level male professional cyclists (26.9 ± 0.4 yrs [mean ± SEM]; V·O_2max: 73.5 ± 0.8 ml · kg^-1 · min^-1). Their results were compared with those of a group of 52 Olympic-class male endurance runners (26.8 ± 0.6 yrs; V·O_2max: 73.3 ± 0.8 ml · kg^-1 · min^-1) and 123 healthy, sedentary male controls. All subjects were Caucasian, and of European ancestry. No significant differences (p > 0.05) were found between groups: RR: 28.5 %; RX: 53.6 % and XX: 17.9 % in controls; RR: 28.0 %; RX: 46.0 % and XX: 26.0 % in cyclists; and RR: 25.0 %; RX: 57.7 %; XX: 17.3 % in runners). No differences were found in indices of endurance performance (VO_2peak or ventilatory thresholds) between athlete carriers of each R577X genotype. In summary, although the α-actinin-3 deficient XX genotype may be detrimental for sprint performance in humans, the R577X polymorphism of the ACTN3 gene does not appear to confer an advantage on the ability of male athletes to sustain extreme endurance performance.

Key words

α-actinin-3 - polymorphism - gene - runners

References

• 1 Bosco C, Montanari G, Ribacchi R, Giovenali P, Latteri F, Iachelli G, Faina M, Colli R, Dal Monte A, La Rosa M. Relationship between the efficiency of muscular work during jumping and the energetics of running.  Eur J Appl Physiol. 1987;  56 138-143
• 2 Clarkson P M, Devaney J M, Gordish-Dressman H, Thompson P D, Hubal M J, Urso M, Price T B, Angelopoulos T J, Gordon P M, Moyna N M, Pescatello L S, Visich P S, Zoeller R F, Seip R L, Hoffman E P. ACTN3 genotype is associated with increases in muscle strength and response to resistance training in women.  J Appl Physiol. 2005;  99 154-163
• 3 Coyle E F, Sidossis L S, Horowitz J F, Beltz J D. Cycling efficiency is related to the percentage of type I muscle fibers.  Med Sci Sports Exerc. 1992;  24 782-788
• 4 Foster C, Hoyos J, Earnest C, Lucia A. Regulation of energy expenditure during prolonged athletic competition.  Med Sci Sports Exerc. 2005;  37 670-675
• 5 Kaneko M. Mechanics and energetics in running with special reference to efficiency.  J Biomech. 1990;  23 (Suppl 1) 57-63
• 6 Larsen H B. Kenyan dominance in distance running.  Comp Biochem Physiol A Mol Integr Physiol. 2003;  136 161-170
• 7 Lucia A, Earnest C, Arribas C. The Tour de France: a physiological review.  Scand J Med Sci Sports. 2003;  13 1-9
• 8 Lucia A, Hoyos J, Santalla A, Earnest C, Chicharro J L. Tour de France versus Vuelta a España: which is harder?.  Med Sci Sports Exerc. 2003;  35 872-878
• 9 Lucia A, San Juan A F, Montilla M, Cañete S, Santalla A, Earnest C, Pérez M. In professional road cyclists, low pedaling cadences are less efficient.  Med Sci Sports Exerc. 2004;  36 1048-1054
• 10 MacArthur D G, North K N. A gene for speed? The evolution and function of α-actinin-3.  BioEssays. 2004;  26 786-795
• 11 Meyer T, Lucia A, Earnest C P, Kindermann W. A conceptual framework for performance diagnosis and training prescription from submaximal gas exchange parameters-theory and application.  Int J Sports Med. 2005;  26 S38-S48
• 12 Mills M, Yang N, Weinberger R, Vander Woude D L, Beggs A H, Easteal S, North K. Differential expression of the actin-binding proteins, α-actinin-2 and - 3, in different species: implications for the evolution of functional redundancy.  Hum Mol Gen. 2001;  10 1335-1346
• 13 Niemi A K, Majamaa K. Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes.  Eur J Hum Genet. 2005;  13 965-969
• 14 North K N, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, Easteal S, Beggs A H. A common nonsense mutation results in α-actinin-3 deficiency in the general population.  Nature Genet. 1999;  21 353-354
• 15 Squire J M. Architecture and function in the muscle sarcomere.  Curr Opin Struct Biol. 1997;  7 247-257
• 16 Williams K R, Cavanagh P R. Relationship between distance running mechanics, running economy, and performance.  J Appl Physiol. 1987;  63 1236-1245
• 17 Yang N, Macarthur D G, Gulbin J P, Hahn A G, Beggs A H, Easteal S H, North K. ACTN3 genotype is associated with human elite athletic performance.  Am J Hum Genet. 2003;  73 627-631
• 18 Yang N, Macarthur D G, Wolde B, Onywera V O, Boit M K, Wilson R H, Scott R A, Pitsiladis Y P, North K. ACTN3 genotype is not associated with elite endurance status in Ethiopians and Kenyans.  Med Sci Sports Exerc. 2005;  37 S472