Genetics of skeletal muscle strength and its determinants in healthy, untrained males

Stebbings, Georgina K. (2015) Genetics of skeletal muscle strength and its determinants in healthy, untrained males. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

It is well accepted that inter-individual variability exists in muscle strength (more specifically maximal voluntary contraction torque), and many of its determinants. The extent of this inter-individual variability, however, has yet to be quantified despite many researchers suggesting genetic factors contribute. The aims of the present thesis were to first quantify the inter-individual variability within skeletal muscle phenotypes in a homogenous population, and secondly to investigate the contribution of multiple genetic polymorphisms to the inter-individual variability within these phenotypes. Genotype and phenotype data was collected from 120 untrained Caucasian males (aged 18-39 yr). Considerable inter-individual variability in muscle strength phenotypes and many of its determinants was observed. Subsequently, polymorphisms in the CNTF, TTN, PTK2, TRHR and ACTN3 genes demonstrated significant associations with one or more of the skeletal muscle phenotypes, but neither ACE nor COL5A1 were found to associate with any of the measured phenotypes. Adopting a polygenic approach that incorporated all of these genetic polymorphisms did not account for the inter-individual variability observed within VL muscle size (inter-individual variability = 13-20%; P ≥ 0.166) or strength (14-19%; P ≥ 0.220). The results identified novel genetic associations between TTN, CNTF and skeletal muscle architecture, in addition to providing the first independent replications of associations between PTK2 and specific force, and TRHR and lean mass. In conclusion, there appears to be a genetic influence on skeletal muscle phenotypes, however, further research is necessary to replicate the associations observed within the current thesis in comparable and different populations. Nonetheless, the work presented here has applications for improving physical performance, in addition to enhancing our understanding of skeletal muscle disorders, which may have implications for how individuals exercise and how skeletal muscle disorders are treated and/or prevented in future.