ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women

Abstract

The alpha-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers, and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3 genotype (R577X) has been found to be associated with performance in Australian elite athletes (Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, and North K. Am J Hum Genet 73: 627-631, 2003). We studied associations between ACTN3 genotype and muscle size [cross-sectional area of the biceps brachii via magnetic resonance imaging (MRI)] and elbow flexor isometric (MVC) and dynamic [1-repetition maximum (1-RM)] strength in a large group of men (N = 247) and women (N = 355) enrolled in a 12-wk standardized elbow flexor/extensor resistance training program of the nondominant arm at one of eight study centers. We found no association between ACTN3 R577X genotype and muscle phenotype in men. However, women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared with heterozygotes (P < 0.05) when adjusted for body mass and age. Women homozygous for the mutant allele (577X) demonstrated greater absolute and relative 1-RM gains compared with the homozygous wild type (RR) after resistance training when adjusted for body mass and age (P < 0.05). There was a trend for a dose-response with genotype such that gains were greatest for XX and least for RR. Significant associations were validated in at least one ethnic subpopulation (Caucasians, Asians) and were independent of training volume. About 2% of baseline MVC and of 1-RM strength gain after training were attributable to ACTN3 genotype (likelihood-ratio test P value, P = 0.01), suggesting that ACTN3 is one of many genes contributing to genetic variation in muscle performance and adaptation to exercise.

ACTN3 R577X polymorphism and team-sport performance: A study involving three European cohorts

“…Approximately 20% of the world population, and 18% of the European population, harbour the ACTN3 577XX genotype and consequently are completely deficient in ␣-actinin-3. 3 The ACTN3 R577X polymorphism has been investigated in the context of human athletic performance, in both elite endurance and power athletes, [4][5][6] and the general population, [7][8][9] with the overall conclusion that ␣-actinin-3 deficiency, as marked by the 577XX genotype, is detrimental to power performance and possibly beneficial to endurance performance. Recently, we have shown, in a large group of elite European athletes (n = 633), that 'worldclass' endurance athletes were 3.7 times more likely to harbour the 577XX genotype than national-level counterparts, and that elite power athletes were ∼50% less likely to harbour the 577XX genotype compared to sedentary controls.…”

Effective utilization of genetic information for athletes and coaches: focus on ACTN3 R577X polymorphism

“…Massidda et al [42] have reported that the ACTN3 R577X genotype accounts for 8.0% of the variation in squat-jump performance of elite soccer players. In the general population, the ACTN3 R577X polymorphism is responsible for 1-2% of the variation in muscle strength [37,43]. These results suggest that the ACTN3 R577X genotype has an apparent contributing role in competitive athletes, particularly elite athletes compared to that in the general population.…”

Endothelial Nitric Oxide Synthase (NOS3) +894 G>T Associates with Physical Activity and Muscle Performance among Young Adults

“…The experimental design of FAMuSS has been described elsewhere [6,[15][16][17][18][19][20][21]. The institutional review boards from the 10 institutions involved with the study approved the study protocol and informed consent was obtained from all individuals prior to enrollment.…”