Is training‐induced increase in muscle mass influenced by ACTN3 genotype?
Authors: Norman Barbara , Psilander Niklas , Lilja Mats , Fernandez‐Gonzalo Rodrigo , Lundberg Tommy 
Published: June 2021

INTRODUCTIONAlpha‐actinin‐3 is a skeletal muscle specific protein. A polymorphism in the ACTN3 gene (R577X) results in lack of alpha‐actinin‐3 protein in skeletal muscle of individuals with XX‐genotype. In sprint/power oriented elite athletes the prevalence of the X‐allele is much lower than in control populations, implying that lack of alpha‐actinin‐3 is detrimental for these athletes. The mechanistic link, however, is not fully established. Actn3 knock‐out mice are shown to have lower muscle mass. We have previously reported that humans with XX‐genotype have lower activation of mTOR‐signaling pathway in response to acute sprint exercise. This may indicate that the XX‐genotype is associated with an attenuated skeletal muscle hypertrophy in response to exercise. The aim of the present study was to examine the impact of ACTN3 genotype on hypertrophy signaling in skeletal muscle and on training‐induced increase in muscle mass.METHODS69 male and female subjects participating in five different longitudinal training studies with different training conditions were investigated. 20 subjects performed 5 weeks of supervised progressive knee‐extensor resistance training (study 1), 16 subjects performed 8 weeks of the same resistance training but with intervention by oral intake of acetylic acid (study 2) and 19 subjects performed 10 weeks of combined leg‐press and knee‐extensor resistance training with one leg (study 3a) followed by a detraining period and a new 5 weeks of the same resistance training but with both legs (pre‐trained leg (study 3b) and previously untrained leg (study 3c)). The volume of m. quadriceps, before and after the training periods, was assessed by MRI (study 1 and 2) or ultrasonography (study 3a, 3b and 3c). Muscle samples obtained in connection with an acute exercise bout in each study were analyzed for phosphorylation of p70S6k by western blot. DNA was extracted from muscle samples and genotyping for the R577X polymorphism was performed by allelic discrimination.RESULTSThe mean relative increase in muscle volume with training was (mean ±SD) 9.7 ±6 % and there was no significant difference between the studies. Therefore the impact of ACTN3 genotype on the training‐induced increase in muscle mass was analyzed in pooled data from all five studies. The relative increase in muscle volume in the different ACTN3 genotypes was (mean ±SD) 10.5 ±6 % in RR, 9.4 ±5 % in RX and 8.4 ±6 % in XX. The acute‐exercise induced increase in relative phosphorylation of p70S6k was (mean ±SD) 25 ±36 % in RR, 14 ±25 % in RX and 10 ±7% in XX. The observed differences between ACTN3‐genotypes were found to be not statistically significant.CONCLUSIONDespite the fact, that the relative increase in muscle volume and phosphorylation of p70S6k was numerically lower in the XX‐genotype as compared to RR and RX, there were no statistically significant differences between the genotypes. Our hypothesis, that ACTN3 genotype is a genetic modifier important for regulation of muscle mass, could thus not be confirmed by a present investigation. A type 2 error cannot be excluded, however, due to, the in general, low relative increase in muscle volume by this type of intervention.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.