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Physiol. Genomics (September 11, 2007). doi:10.1152/physiolgenomics.00173.2007
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Submitted on August 1, 2007
Accepted on September 11, 2007

The ACTN3 (R577X) genotype is associated with fiber type distribution

Barbara Vincent1, Katrien De Bock1, Monique Ramaekers1, Els Van den Eede1, Marc Van Leemputte1, Peter J. Hespel2, and Martine Thomis1*

1 Department of Biomedical Kinesiology, FaBeR-K.U.Leuven, Leuven, Vlaams-Brabant, Belgium
2 Department of Biomedical Kinesiology, FaBeR - K.U.Leuven, Leuven, Belgium

* To whom correspondence should be addressed. E-mail: martine.thomis{at}faber.kuleuven.be.

Alpha-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 {alpha}-actinin-3 deficiency in XX homozygotes. Former studies reported a strong association between the R577X polymorphism and elite athletes’ muscle-power performance. 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. 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 yr) 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 to XX carriers (p<0.05). Fiber type characteristics differed significantly between the two genotype groups. The percentage surface and number of type IIx fibers was greater in the RR than the XX genotype group (p<0.05), and {alpha}-actinin-3 protein content is systematically higher in type IIx compared to type IIa fibers (staining intensity ratio IIx/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.







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Copyright © 2007 by the American Physiological Society.