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.

MMP‐3 (–1171 5A/6A; Lys45Glu) variants affect serum levels of matrix metalloproteinase (MMP)‐3 and correlate with severity of COPD: A study of MMP‐3, MMP‐7 and MMP‐12 in a Tunisian population

“…revealed that the G allele of lys45Glu and the 6A allele of (–1171) 5A/6A variants associate with the highest level of circulating MMP‐3 in patients with rheumatoid arthritis. The results of the present study also agree with those of Foster et al . suggesting that the G variant of Lys45Glu SNP may promote elevated levels of MMP‐3 expression via increased MMP‐3 activation as a result of an altered interaction with other amino acids in the propeptide region.…”

MMP3 and TIMP2 gene variants as predisposing factors for Achilles tendon pathologies: Attempted replication study in a British case–control cohort

“…In an earlier study we found that the GG genotype was a risk factor for Achilles tendinopathy but not Achilles tendon rupture in South Africans Caucasians ( Raleigh et al, 2009 ). The G allele of the rs679620 locus is known to increase MMP3 expression ( Foster et al, 2012 ), as it is in high linkage disequilibrium (LD) with the 5A allele of the rs3025058 variant ( Chen et al, 2012 ). The 5A allele has been reported to up-regulate MMP3 mRNA levels ( Ye, 2006 ).…”

Effect of 6-Month Fascia-Oriented Training on Jump Performance in Elite Female Volleyball Players

“…There are many non-genetic factors infl uencing fascial tissues. Many of these are primarily conditioned by genetic predispositions anyway (Foster, 2012). The determination of genetic factors is a complex problem whose analysis was not the aim of this study.…”