The R577x Polymorphism In The Actn3 Gene Is Associated With Muscle Strength In Women

Abstract

PURPOSE Alpha-actinin-3 (ACTN3) is a structural protein of the sarcomeric Z-line that is specifically expressed in Type II muscle fibers. ACTN3 is important for anchoring actin and playing a regulatory function in coordinating muscle fiber contraction. ACTN3 is absent in ∼18% of healthy white individuals with homozygosity of a common stop codon, R577X, in the ACTN3 gene. The ACTN3 R577X polymorphism has been associated with elite athletic performance, but its role in normal variation in muscle function has not been established. Given the localization of ACTN3 in fast twitch skeletal muscle fibers, and the importance of type II fibers for force generating capacity, we hypothesized that individuals deficient in ACTN3 (X-allele homozygotes) would display lower levels of muscle strength compared to R-allele carriers (R/R + R/X) with the ACTN3 protein. METHODS 408 Caucasian volunteers (215 men and 193 women) aged 22–90 years were genotyped to determine the presence of the R allele using standard techniques. Knee extensor (KE) concentric and eccentric peak torque values were determined using isokinetic dynamometry and fat free mass was determined by dual-energy X-ray absorptiometry. RESULTS Sample sizes by genotype group were: X/X=86, X/R+R/R=322 (men: X/X=46, X/R+R/R=169, women: X/X=40, X/R+R/R=153). Women deficient in ACTN3 (X/X) displayed lower KE concentric peak torque (30°/sec: 110.7 ± 4.3 vs. 120.7 ± 2.2 Nm, p<0.05; 180°/sec: 70.1 ± 2.9 vs. 77.9 ± 1.5 Nm, p<0.05) and KE eccentric peak torque (30°/sec: 140.9 ± 5.7 vs. 156.1 ± 2.8 Nm, p<0.05) than R-allele carriers. Differences in strength can be explained by fat free mass differences, women deficient in ACTN3 (X/X) also displayed lower levels of fat free mass (39 ± 5.9 vs. 40.4 ± 3.1 kg, p<0.05) than R-allele carriers. No significant differences in strength or fat free mass were observed in men. CONCLUSION Our results indicate that the absence of ACTN3 influences KE strength in women but not men across the adult age span. Strength differences observed between genotype groups in women can partially be explained by differences in fat free mass. Supported by intramural NIH-NIA funds, AG21500 and AG22791.