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J Appl Physiol 99: 154-163, 2005. First published February 17, 2005; doi:10.1152/japplphysiol.01139.2004
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ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women

Priscilla M. Clarkson,1 Joseph M. Devaney,2 Heather Gordish-Dressman,2 Paul D. Thompson,3 Monica J. Hubal,1 Maria Urso,1 Thomas B. Price,3,4 Theodore J. Angelopoulos,5 Paul M. Gordon,6 Niall M. Moyna,7 Linda S. Pescatello,8 Paul S. Visich,9 Robert F. Zoeller,10 Richard L. Seip,3 and Eric P. Hoffman2

1Department of Exercise Science, University of Massachusetts, Amherst, Massachusetts; 2Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC; 3Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, Connecticut; 4Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut; 5Child, Family and Community Sciences, University of Central Florida, Orlando, Florida; 6Division of Exercise Physiology, School of Medicine, West Virginia University, Morgantown, West Virginia; 7Department of Sport Science and Health, Dublin City University, Dublin, Ireland; 8School of Allied Health, University of Connecticut, Storrs, Connecticut; 9Human Performance Laboratory, Central Michigan University, Mount Pleasant, Michigan; and 10Department of Exercise Science and Health Promotion, Florida Atlantic University, Davie, Florida

Submitted 11 October 2004 ; accepted in final form 9 February 2005

The {alpha}-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers, and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3 genotype (R577X) has been found to be associated with performance in Australian elite athletes (Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, and North K. Am J Hum Genet 73: 627–631, 2003). We studied associations between ACTN3 genotype and muscle size [cross-sectional area of the biceps brachii via magnetic resonance imaging (MRI)] and elbow flexor isometric (MVC) and dynamic [1-repetition maximum (1-RM)] strength in a large group of men (N = 247) and women (N = 355) enrolled in a 12-wk standardized elbow flexor/extensor resistance training program of the nondominant arm at one of eight study centers. We found no association between ACTN3 R577X genotype and muscle phenotype in men. However, women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared with heterozygotes (P < 0.05) when adjusted for body mass and age. Women homozygous for the mutant allele (577X) demonstrated greater absolute and relative 1-RM gains compared with the homozygous wild type (RR) after resistance training when adjusted for body mass and age (P < 0.05). There was a trend for a dose-response with genotype such that gains were greatest for XX and least for RR. Significant associations were validated in at least one ethnic subpopulation (Caucasians, Asians) and were independent of training volume. About 2% of baseline MVC and of 1-RM strength gain after training were attributable to ACTN3 genotype (likelihood-ratio test P value, P = 0.01), suggesting that ACTN3 is one of many genes contributing to genetic variation in muscle performance and adaptation to exercise.

quantitative trait loci; muscle genetics; alpha-actinin


Address for reprint requests and other correspondence: P. M. Clarkson, Dept. of Exercise Science, 110 Totman Bldg., Univ. of Massachusetts, Amherst, MA 01003 (E-mail: clarkson{at}excsci.umass.edu)




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