ACTN3 genotype influences exercise-induced muscle damage during a marathon competition



Exercise-induced muscle damage has been identified as one of the main causes of the progressive decrease in running and muscular performance in marathoners. The aim of this investigation was to determine the influence of the ACTN3 genotype on exercise-induced muscle damage produced during a marathon.


Seventy-one experienced runners competed in a marathon race. Before and after the race, a sample of venous blood was obtained and maximal voluntary leg muscle power was measured during a countermovement jump. In the blood samples, the ACTN3 genotype (R577X) and the changes in serum creatine kinase and myoglobin concentrations were measured. Data from RX heterozygotes and XX mutant homozygotes were grouped as X allele carriers and compared to RR homozygotes.


At the end of the race, X allele carriers presented higher serum myoglobin (774 ± 852 vs 487 ± 367 U L−1; P = 0.02) and creatine kinase concentrations (508 ± 346 vs 359 ± 170 ng mL−1; P = 0.04) than RR homozygotes. Pre-to-post-race maximal voluntary leg muscle power reduction was more pronounced in X allele carriers than RR homozygotes (−34.4 ± 16.1 vs −27.3 ± 15.4%; P = 0.05). X allele carriers self-reported higher levels of lower limb muscle pain (7 ± 2 vs 6 ± 2 cm; P = 0.02) than RR homozygotes at the end of the race.


In comparison to RR homozygotes, X allele carriers for the R577X polymorphism of the ACTN3 gene presented higher values for typical markers of exercise-induced muscle damage during a competitive marathon. Thus, the absence of a functional α-actinin-3 produced by the X allele might induce higher levels of muscle breakdown during prolonged running events.

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Fig. 1
Fig. 2



Percentage of difference


α-Actinin-2 gene


α-Actinin-3 gene


Arbitrary units


Deoxyribonucleic acid


Effect size


Polymerase chain reaction


Single-nucleotide polymorphism


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The authors wish to thank the participants in this study for their invaluable contribution. In addition, we are very grateful to the Organization of Rock ‘n’ Roll Madrid Marathon and ½ for their help in setting the investigation areas at the start and finish lines.

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Correspondence to Juan Del Coso.

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The authors declare that they have no conflict of interest derived from the outcomes of this study.

Financial support

The study was part of the DAMUS project supported by a Grant-in-aid from the Vice-Rectorate of Research and Science, at the Camilo Jose Cela University.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Communicated by Fabio Fischetti.

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Del Coso, J., Valero, M., Salinero, J.J. et al. ACTN3 genotype influences exercise-induced muscle damage during a marathon competition. Eur J Appl Physiol 117, 409–416 (2017).

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  • α-Actinins
  • Rhabdomyolysis
  • Muscle pain
  • Endurance exercise
  • Genetics
  • Single-nucleotide polymorphism.