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1 Exercise Science, University of Massachusetts, Amherst, MA, USA
2 Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA
3 United States Army Research Institute of Environmental Medicine, Natick, MA, USA
* To whom correspondence should be addressed. E-mail: clarkson{at}excsci.umass.edu.
Strenuous exercise results in damage to skeletal muscle that is manifested in delayed muscle pain, prolonged strength loss, and increases in muscle proteins in the blood, especially creatine kinase (CK) and myoglobin (Mb). Some individuals experience profound changes in these variables in response to standard laboratory exercise or recreational activities. We proposed that variations in genes coding for two myofibrillar proteins (alpha-actinin 3 (ACTN3) and myosin light chain kinase (MLCK)) may explain the large variability in the response to muscle-damaging exercise. We hypothesized that subjects with specific single nucleotide polymorphisms (SNPs) in ACTN3 and MLCK would show a greater loss in muscle strength and/or a greater increase in blood CK and Mb in response to eccentric exercise. Blood from 157 subjects who performed a standard elbow flexion eccentric exercise protocol was tested for association between genotypes of ACTN3 (1 SNP tested; R577X) and MLCK (2 SNPs tested; C49T and C37885A) and changes in blood CK and Mb and isometric strength. Subjects possessing the ACTN3-deficienct genotype (XX) had lower baseline CK compared to the heterozygotes (p=0.035). Following the eccentric exercise, those subjects homozygous for the MLCK 49T rare allele had a significantly greater increase in CK and Mb (p<0.01) compared with the heterozygotes, and those heterozygous for MLCK C37885A had a significantly greater increase in CK compared with the homozygous wildtype (p<0.05). There was only one subject homozygous for the rare MLCK C37885A allele. MLCK C37885A was also associated with post-exercise strength loss (p<0.05); the heterozygotes demonstrated greater strength loss compared with the homozygous wild type (CC). These results show that variations in genes coding for specific myofibrillar proteins influence phenotypic responses to muscle damaging exercise.
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