Genetic Variation, Protein Composition and Potential Influences on Tendon Properties in Humans

ABSTRACT

Sequence variations in genes that code for proteins involved in homeostatic processes within tendons may influence tendon mechanical properties. Since variants of the four genes COL5A1, TNC, MMP3 and GDF5 have been implicated in the aetiopathogenesis of tendinopathies, which is ultimately characterised by abnormal structural and regulatory processes, sequence variations in these four genes may also influence how the tendon functions mechanically, even in the absence of tendinopathy. For example, two reports of association between variation in the COL5A1 gene and measures of flexibility complement reported associations between genotype and incidence of tendinopathy. Non-genetic factors such as age, body mass and physical activity status influence risk of tendon injury and physical performance potential independently from genomics, and also in gene-environment interactions. However, these non-genetic factors are often not considered in genetic association studies, probably due to their retrospective nature. Further research examining COL5A1, TNC, MMP3 and GDF5, as well as other genes that may influence the maintenance of tendon homeostasis such as COL1A1 which regulates the production of collagen type 1, the most abundant structural component of tendon is encouraged. Establishing the genetic basis of tendon properties in asymptomatic populations may advance understanding of some aspects relevant to physical performance and of the aetiology of tendinopathies. To improve understanding, accurate and reproducible assessments of tendon properties are required. However, no valid and reliable assessments of tendon properties, such as those involving in vivo ultrasound imaging techniques, have yet been applied to genetic association studies in humans.