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ACTN3 R577X polymorphism is associated with jumping performance and athletes with RR genotype have better scores in tests than athletes with XX or RX genotype independently of the sport discipline. MATERIALS AND METHODS: Two hundred young Polish male participants representing different disciplines were recruited for this study. Genotyping for ACTN3 gene was performed using polymerase chain reaction. The power output of lower extremities and the height of rise of the body mass center during vertical jumps were measured on a force plate. RESULTS: The genotype distribution of the ACTN3 gene did not differ significantly between groups of athletes. The significant difference in height of counter-movement jump was found between athletes with RR and XX genotype (0.446+/-0.049m vs. 0.421+/-0.036m, respectively, P=0.026). The ACTN3 RR genotype was associated with greater muscle power and height of jump in young male athletes. CONCLUSIONS: These results suggest that the ACTN3 gene may play a significant role in determining muscle phenotypes. However, this gene is only one of many factors which could contribute to athletes' performance and muscle phenotypes.

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eficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more "energy efficient" in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR) are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i) an increased rate of decay of the twitch transient; (ii) a fourfold increase in the rate of SR Ca2+ leak; (iii) a threefold increase in the rate of SR Ca2+ pumping; and (iv) enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments during recent evolution.

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ion. The sarcomeric alpha-actinins were originally characterised as scaffold proteins at the muscle Z-line. Through studying the Actn3 knockout mouse and alpha-actinin-3 deficient humans, significant progress has been made in understanding how ACTN3 genotype alters muscle function, leading to an appreciation of the diverse roles that alpha-actinins play in muscle. The alpha-actinins interact with a number of partner proteins, which broadly fall into three biological pathways-structural, metabolic and signalling. Differences in functioning of these pathways have been identified in alpha-actinin-3 deficient muscle that together contributes to altered muscle performance in mice and humans. Here we discuss new insights that have been made in understanding the molecular mechanisms that underlie the consequences of alpha-actinin-3 deficiency.