ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women

1 Department of Exercise Science, University of Massachusetts, Amherst, Massachusetts; 2 Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC; 3 Division of Cardiology, Henry Low Heart Center, Hartford Hospital, Hartford, Connecticut; 4 Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut; 5 Child, Family and Community Sciences, University of Central Florida, Orlando, Florida; 6 Division of Exercise Physiology, School of Medicine, West Virginia University, Morgantown, West Virginia; 7 Department of Sport Science and Health, Dublin City University, Dublin, Ireland; 8 School of Allied Health, University of Connecticut, Storrs, Connecticut; 9 Human Performance Laboratory, Central Michigan University, Mount Pleasant, Michigan; and 10 Department of Exercise Science and Health Promotion, Florida Atlantic University, Davie, Florida Submitted 11 October 2004 ; accepted in final form 9 February 2005 The -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