The Actn3 Gene R577X Polymorphism Is Associated With Muscle Power Response To Strength Training

Abstract

Alpha-actinin-3 (ACTN3) is a Z-disc structural protein found only in Type 2 muscle fibers. The less common X-allele of the R577X polymorphism in the ACTN3 gene results in a premature stop codon and alpha-actinin-3 protein deficiency in X/X homozygotes. A strong association has been reported between the R577X polymorphism and elite athletic performance, especially in muscle power-related events. PURPOSE We sought to clarify the association of the R577X polymorphism and muscle function by studying muscle-related variables in older men and women in response to strength training (ST). METHODS A total of 102 older men and women (67 yr., range: 52–83 yr.) were genotyped for the R577X polymorphism using standard techniques. Knee extensor muscle strength was measured using one-repetition maximum (1RM) and isokinetic dynamometry (Kin-Com), muscle power was measured using a customized knee extensor dynamometer (Keiser; total n = 58), and quadriceps muscle volume was measured using CT. All subjects underwent 10 wk (3 day/wk) of unilateral high-volume, heavy-resistance knee extensor ST. RESULTS No genotype differences were observed at baseline for any muscle phenotypes in either men or women. In response to ST, men with either the X/X (n = 4) or R/X (n = 11) genotype demonstrated significantly lower increases in relative peak muscle power than the R/R (n = 7) genotype group (9±49 vs. 52±39 vs. 239±37 W, respectively; p < 0.01). These genotype differences remained significant after correcting for the change in muscle volume (p < 0.01). Similarly, male carriers of the X-allele (R/X + X/X genotypes) demonstrated significantly and substantially lower improvements in relative peak power (40±31 vs. 239±37 W, p < 0.01), absolute peak power (90±27 vs. 235±87 W, p < 0.05), and absolute peak movement velocity (0.30±0.10 vs. 0.94±0.30 rad/sec, p < 0.05) compared to R/R homozygotes. No such differences in muscle training response were observed in women for any variables. CONCLUSION These data support existing evidence of an association of the ACTN3 gene with elite athletic performance by showing that the ACTN3 R577X polymorphism is associated with the response of muscle power to ST in men. The ACTN3 R577X polymorphism represents one of the first genetic associations specific to the response of skeletal muscle to strength training. Supported by R01 AG18336, R01 AG21500, and K01 AG22791.