SummaryCOL5A1 encodes for the α1 chain of type V collagen, an important regulator of fibril assembly in tendons, ligaments and other connective tissues. A polymorphism (rs12722) within the functional COL5A1 3 -untranslated region (UTR) has been shown to associate with chronic Achilles tendinopathy and other exercise-related phenotypes. The COL5A1 3 -UTR contains several putative cis-acting elements including a functional Hsa-miR-608 binding site. The aim of this study was to determine whether previously uncharacterized polymorphisms within a functional region of the COL5A1 3 -UTR or the MIR608 gene are associated with chronic Achilles tendinopathy. The effect of these COL5A1 3 -UTR polymorphisms on the 3 -UTR predicted mRNA secondary structure was also investigated. One hundred and sixty Caucasian chronic Achilles tendinopathic and 342 control participants were genotyped for the COL5A1 3 -UTR markers rs71746744, rs16399 and rs1134170, as well as marker rs4919510 within MIR608. All four genetic markers were independently associated with chronic Achilles tendinopathy. The COL5A1 polymorphisms appear to alter the predicted secondary structure of the 3 -UTR. We propose that the secondary structure plays a role in the regulation of the COL5A1 mRNA stability and by implication type V collagen production.

MicroRNAs are small non-coding regulatory RNAs which may be released into the systemic circulation as a consequence of the body's adaptation to exercise. The expression profile of circulating miRNAs (ci-miRNAs) has been proposed as a potential diagnostic biomarker for adaptive responses of particular systems to physical exertion. Several miRNAs are recognized as regulators of signalling pathways such as the IGF1/PI3K/AKT/mTOR axis, relevant to exercise adaptation. MicroRNA levels may fluctuate depending on training type/exercise regimen in correlation with phenotypic features such as VO2 max. Muscle-specific miRNAs have been proposed as regulators of skeletal muscle/myocardial interactions during physical exertion, thereby facilitating adaptation. Differential expression of miRNAs may relate to molecular patterns of communication triggered during/after exercise as response, recovery and adaptation mechanisms to training load. This review highlights recent findings and the potential significance of specific miRNAs in the process of exercise adaptation. Altered ci-miRNA profiles following exercise suggest that they may be useful biomarkers of health and adaptation to intervention strategies. Identification of the concert of miRNA expression signatures together with their targets is critical towards understanding gene regulation in this context. Understanding how the external environment influences gene expression via miRNAs will provide insight into potential therapeutic target strategies for disease.

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