ACTN3 Genotype Affects Change in Muscle Fiber Cross-Sectional Area from Adolescence to Adulthood

Abstract

INTRODUCTION: Alpha-actinin-3 is a Z-disc protein that is expressed only in type II muscle fibers. Common null polymorphism in the ACTN3 gene (R577X) results in lack of this protein in XX-genotypes. In sprint/power oriented elite athletes the prevalence of the X-allele is much lower than in control populations. That implies that lack of alpha-actinin-3 is detrimental for these athletes but a mechanistic link is not fully established. We have previously shown that ACTN3 genotype modulates skeletal muscle hypertrophy signaling in response to sprint exercise in moderately trained subjects. PURPOSE: To examine the impact of ACTN3 genotype on changes in fiber dimensions from adolescence to adulthood. METHODS: 63 male and female subjects (13 XX, 29 RX, 21 RR) from the general Swedish population were studied at 16 and 27 years of age. Their physical activity level was estimated by a questionnaire. Muscle samples were obtained from vastus lateralis muscle by needle biopsy technique. The samples were analyzed histochemically for fiber types (I, IIA, IIB). Cross-sectional area (CSA) of the different fiber types was measured from histological sections by planimetry. DNA was extracted from muscle samples and the genotyping was performed by allelic discrimination. Statistical analyses of the effect of ACTN3 and sex on changes in CSA with age were performed by ANOVA and multiple regression analysis. RESULTS: A significant difference in the relative change of CSA with age, across ACTN3 genotypes was observed in type IIA fibers (ANOVA P=0.02) but not in type I fibers and type IIB fibers. The change, expressed as 27-16 years/16-years value, was in type IIA fibers -4.2%, -2.5% and 7.7% in XX, RX and RR respectively and in type IIB -3.0%, -3.4%, and 9.9% in XX, RX and RR respectively. Multiple regression analysis showed that the change in CSA of type IIA fibers was dependent on ACTN3 genotype, while the change in CSA of type IIB was equally dependent on ACTN3 genotype and sex. No ACTN3 genotype effect was observed for the CSA change in type I fibers where alpha-actinin-3 is not expressed. No significant differences in CSA were detected across ACTN3 genotypes either at 16 or 27 years. CONCLUSION: ACTN3 genotype is strongly suggested to be a determinant of dimensions of type II skeletal muscle fibers in humans which supports the findings in ACNT3 knock out mice.