α-Actinin-3 is a Z-disc structural protein found only in type II muscle fibers. The X allele of the R577X polymorphism in the ACTN3 gene results in a premature stop codon and α-actinin-3 deficiency in XX homozygotes. Associations between the R577X polymorphism and the muscle-power performance of elite athletes have been described earlier. About 45% of the fiber type proportions are determined by genetic factors. The ACTN3 variant could be one of the contributing genes in the heritability of fiber type distribution through its interaction with calcineurin. The aim of this study was to quantify the association between the polymorphism and muscle fiber type distribution and fast-velocity knee extension strength. Ninety healthy young men (18–29 y) were genotyped for ACTN3 R577X. Knee extensor strength was measured isometrically (45°) and at different dynamic velocities (100–300°/s) on a programmable dynamometer. Twenty-two XX and twenty-two RR subjects underwent a biopsy of the right vastus lateralis muscle. Fiber type composition was determined by immunohistochemistry. Homozygotes for the R allele show significantly higher relative dynamic quadriceps torques at 300°/s, compared with XX carriers ( P < 0.05). Fiber type characteristics differed significantly between the two genotype groups. The percentage surface and number of type IIx fibers were greater in the RR than the XX genotype group ( P < 0.05), and α-actinin-3 protein content is systematically higher in type IIx compared with type IIa fibers (staining intensity ratio IIx to IIa = 1.17). This study shows that the mechanism, by which the ACTN3 polymorphism has its effect on muscle power, might rely on a control function of fiber type proportions.

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II_A muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Background: The increasing age of coronary artery disease (CAD) patients and the occurrence of sarcopenia in the elderly population accompanied by 'fear of moving' and hospitalization in these patients often results in a substantial loss of skeletal muscle mass and muscle strength. Cardiac rehabilitation can improve exercise tolerance and muscle strength in CAD patients but less data describe eventual morphological muscular changes possibly by more difficult access to imaging techniques. Therefore the aim of this study is to assess and quantify the reliability and validity of an easy applicable method, the ultrasound (US) technique, to measure the diameter of rectus femoris muscle in comparison to the muscle dimensions measured with CT scans. Methods: 45 older CAD patients without cardiac event during the last 9 months were included in this study. 25 patients were tested twice with ultrasound with a two day interval to assess test-retest reliability and 20 patients were tested twice (once with US and once with CT) on the same day to assess the validity of the US technique compared to CT as the gold standard. Isometric and isokinetic muscle testing was performed to test potential zero-order correlations between muscle diameter, muscle volume and muscle force. Results: An intraclass correlation coefficient (ICC) of 0.97 ((95%CL: 0.92 - 0.99) was found for the test-retest reliability of US and the ICC computed between US and CT was 0.92 (95%CL: 0.81 - 0.97). The absolute difference between both techniques was 0.01 ± 0.12 cm (p = 0.66) resulting in a typical percentage error of 4.4%. Significant zero-order correlations were found between local muscle volume and muscle diameter assessed with CT (r = 0.67, p = 0.001) and assessed with US (r = 0.49, p < 0.05). Muscle strength parameters were also significantly correlated with muscle diameter assessed with both techniques (range r = 0.45-r = 0.61, p < 0.05). Conclusions: Ultrasound imaging can be used as a valid and reliable measurement tool to assess the rectus femoris muscle diameter in older CAD patients.