ACTN3genotype and modulation of skeletal muscle response to exercise in human subjects

Abstract

α-Actinin-3 is a Z-disc protein expressed only in type II muscle fibers. A polymorphism in the ACTN3 gene (R577X) results in lack of α-actinin-3 in XX genotype. The prevalence of the mutated X-allele is lower among power/sprint oriented athletes compared with controls, indicating that the lack of α-actinin-3 is detrimental in these sports, but a mechanistic link has not been established. Results from Actn3-knockout (KO) mouse model suggest that α-actinin-3 may affect muscle mass and muscle glycogen levels. In the present investigation we examined muscle fiber type composition, cross-sectional fiber area (CSA), and muscle glycogen levels at baseline in 143 human subjects with different ACTN3 genotypes. In addition, hypertrophy signaling and glycogen utilization in response to sprint exercise were studied in a subset of subjects. Glycogen utilization was analyzed in separate pools of type I and type II fibers. No differences in fiber type composition, CSA, or muscle glycogen levels were observed at baseline across the ACTN3 genotypes. However, the sprint exercise-induced increase in phosphorylation of mTOR and p70S6k was smaller in XX than in RR+RX (P = 0.03 and P = 0.01, respectively), indicating a less pronounced activation of hypertrophy signaling in XX. Glycogen utilization during sprint exercise varied across ACTN3 genotypes in type II fibers (P = 0.03) but not in type I fibers (P = 0.38). The present results are in accordance with findings from the KO mice and reinforce the hypothesis that ACTN3 genotype-associated differences in muscle mass and glycogen utilization provide a mechanistic explanation for the modulation of human performance by the ACTN3 genotype.

Associação de polimorfismos genéticos com capacidades físicas e composição corporal em idosas

“…It is noteworthy that the differences between results found in this study and those of literature may be related to differences in the age group studied, test protocols used, countries of origin and level of physical activity of participants 13,27 , and in the future it would be interesting to analyze whether there is variation in gene and protein expression of ACE and ACTN3 in different age groups and subjects with different levels of physical activity, despite the difficulty in obtaining the tissues in which these genes are expressed (kidneys and lungs for ACE and skeletal muscles for ACTN3), which would help in the understanding of our results. In addition, the number of individuals in our study, as well as in studies used for discussion, can be considered a limiting factor due to the importance of a large number of subjects in studies with population genetics.…”

“…Individuals who have the XX genotype have lack of ACTN3, while heterozygotes (RX genotype) have fewer amount of ACTN3, but no disease 10 . ACTN3 is found in fast-twitch fibers (type II), suggesting that R577X polymorphism is related to functionality, power and muscle strength 11 , as shown by Kim et al 12 , who found lower frequency of XX genotype for the ACTN3 gene in elite athletes compared with non-athletes and also by Norman et al 13 , who showed that individuals with XX genotype for the ACTN3 gene have lower signaling for metabolic pathways associated with hypertrophy and less use of muscle glycogen during exercise. Thus, those who express ACTN3 (RX or RR genotypes) have advantage in activities that require strength or muscle power, while those who do not express ACTN3 (XX genotype) have advantage in predominantly aerobic activities.…”

“…Regarding the aerobic capacity, literature points to a predisposition to better aerobic capacity of allele X of ACTN3 gene in adults 11,13,27 . However, no studies were found in literature associating flexibility with R577X polymorphism for the ACTN3 gene, as well as studies associating flexibility with aerobic capacity in the elderly.…”

Association of ACTN3 polymorphisms with BMD, and physical fitness of elderly women

“…Previous studies have reported an association between the RR genotype of the ACTN3 R577X polymorphism and muscle power in elite athletes22 ) and ordinary people23 ) . In particular, the XX genotype is lower among power/sprint-oriented athletes than the RR genotype24 ) , and this finding is supported by the observation that individuals with the XX genotype show lower thigh muscle cross-sectional area than those with the RR and RX genotypes14 ) . However, considering the role of ACTN3 in skeletal muscle, and consequentially muscle strength and endurance, the present study surprisingly found no such relationship.…”

Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) Gene in Osteocytes Stimulates Soleus Muscle Regeneration and Increased Size and Contractile Force with Age

“…For example, expression of actinin3, titin, and desmin is increased compared with controls. Z-disc component actinin3 is strongly associated with improvements in sprint or endurance (72,73), whereas titin is also localized to the Z-disc, which mechanically couples sarcomeric contraction and stretching (74,75). Desmin is required for the tensile strength and integrity of myofibrils (76).…”