ACTN3 R577X Genotype and Exercise Phenotypes in Recreational Marathon Runners

Abstract

Background: Homozygosity for the X-allele in the ACTN3 R577X (rs1815739) polymorphism results in the complete absence of α-actinin-3 in sarcomeres of fast-type muscle fibers. In elite athletes, the ACTN3 XX genotype has been related to inferior performance in speed and power-oriented sports; however, its influence on exercise phenotypes in recreational athletes has received less attention. We sought to determine the influence of ACTN3 genotypes on common exercise phenotypes in recreational marathon runners. Methods: A total of 136 marathoners (116 men and 20 women) were subjected to laboratory testing that included measurements of body composition, isometric muscle force, muscle flexibility, ankle dorsiflexion, and the energy cost of running. ACTN3 genotyping was performed using TaqMan probes. Results: 37 runners (27.2%) had the RR genotype, 67 (49.3%) were RX and 32 (23.5%) were XX. There was a difference in body fat percentage between RR and XX genotype groups (15.7 ± 5.8 vs. 18.8 ± 5.5%; effect size, ES, = 0.5 ± 0.4, p = 0.024), whereas the distance obtained in the sit-and-reach-test was likely lower in the RX than in the XX group (15.3 ± 7.8 vs. 18.4 ± 9.9 cm; ES = 0.4 ± 0.4, p = 0.046). Maximal dorsiflexion during the weight-bearing lunge test was different in the RR and XX groups (54.8 ± 5.8 vs. 57.7 ± 5.1 degree; ES = 0.5 ± 0.5, p = 0.044). Maximal isometric force was higher in the RR than in the XX group (16.7 ± 4.7 vs. 14.7 ± 4.0 N/kg; ES = −0.5 ± 0.3, p = 0.038). There was no difference in the energy cost of running between genotypes (~4.8 J/kg/min for all three groups, ES ~0.2 ± 0.4). Conclusions: The ACTN3 genotype might influence several exercise phenotypes in recreational marathoners. Deficiency in α-actinin-3 might be accompanied by higher body fatness, lower muscle strength and higher muscle flexibility and range of motion. Although there is not yet a scientific rationale for the use of commercial genetic tests to predict sports performance, recreational marathon runners who have performed such types of testing and have the ACTN3 XX genotype might perhaps benefit from personalized strength training to improve their performance more than their counterparts with other ACTN3 genotypes.

Influence of the ACTN3 R577X genotype on the injury epidemiology of marathon runners

“…The questionnaire was based on the consensus statement on injury definitions and data collection in epidemiological studies in athletics [27]. The effect of the ACTN3 R577X genotype in several exercise phenotypes such as anthropometry, force production, muscle flexibility and energy cost of running has been recently published using a subset of the individuals included in this investigation [15].…”

“…A recent investigation with amateur marathon runners found that XX individuals produce less muscle force, have lower thigh fat-free mass volume and have higher percentages of body fat [15] than RR counterparts. In contrast, runners with the XX genotype had higher muscle flexibility and ankle dorsiflexion than runners with the RR or RX genotype [15].…”

“…A recent investigation with amateur marathon runners found that XX individuals produce less muscle force, have lower thigh fat-free mass volume and have higher percentages of body fat [15] than RR counterparts. In contrast, runners with the XX genotype had higher muscle flexibility and ankle dorsiflexion than runners with the RR or RX genotype [15]. These data suggest that α-actinin-3 deficiency, due to XX homozygosity in the ACTN3 R577X polymorphism, might induce both positive and negative phenotypes for endurance running contributing to an explanation for why a loss-of-function genetic variant has been positively selected through evolution.…”

Genetic and Epigenetic Modulation of Cell Functions by Physical Exercise

“…On the other hand, the ability to perform PA can be influenced by the genotype. In one of the original papers published in this Special Issue, Del Coso and co-workers [21] analyzed the exercise phenotypes of recreational marathon runners endowed with different variants of the gene encoding α-actinin-3 (ACTN3). Normally, the expression of this protein is limited to fast-type muscle fibers.…”

“…It was reported that the ACTN3 genotype might influence exercise phenotypes in recreational marathoners [22]. In particular, deficiency of α-actinin-3 seems to correlate with higher body fatness, lower muscle strength, and higher muscle flexibility [21].…”