Polymorphisms within the COL5A1 3’- UTR that alters mRNA structure and the MIR608 gene are associated with Achilles Tendinopathy
Abrahams Y., Laguette MJ., Prince S., Collins M. Annals of Human Genetics. 2013; 1-11
Take Home Message: Chronic Achilles tendinopathy is related to variations of genes that may influence tendon development and composition.
Many of us have been taught that repetitive overuse may lead to changes in tendon structure and composition (tendon degeneration). But, we have also seen articles on SMR that suggest Achilles tendinopathy may be related to genetic variations (polymorphisms), which may contribute to different tendon structure or composition. If we can confidently identify which variations increase the risk of tendinopathy then this may allow us identify high-risk patients that would benefit from overuse-injury prevention programs. Therefore, the purpose of this study was to expand on prior research and determine if 4 genetic variations were related to chronic Achilles tendinopathy. The authors extracted DNA and genotyped 3 variations within a gene for a type of collagen (COL5A1 gene) as well as a variation in a gene for a protein that regulates collagen production (MIR608 gene). The study included 342 asymptomatic control participants and 160 participants diagnosed with chronic Achilles tendinopathy. The authors found that the odds of having each of these 4 variations were 1.6 to 2.0 times greater among participants with chronic Achilles tendinopathy compared to the healthy controls. Participants with chronic Achilles tendinopathy were also 2.6 times more likely to have all 4 variations. The authors also determined that genetic variations within the region of interest on the collagen gene could produce significant structural changes to proteins associated with its gene expression.
This study introduces 3 more polymorphisms within this collagen gene that are associated with tendinopathies. Collagen exists in every musculoskeletal tissue; therefore if these polymorphisms could affect the Achilles tendon they could also be associated with other tendon alterations. Previously, some of these polymorphisms were associated with mechanically weak tendons. This suggests that these variations influence collagen assembly (structural strength) during development, which may later influence an individual’s susceptibility to chronic tendinopathies. This may also be the case for variations in the MIR608 gene since this gene aids in the production and assembly of collagen within tendon. Finally, the authors found a gene-gene interaction, which suggests that having variations in both genes could affect the structural integrity of the tendon, possibly even more so than having just one gene affected Although this study found an association between several polymorphisms and chronic Achilles tendinopathy, there have been many studies and several other genes found to have an association with chronic Achilles tendinopathy. Therefore, this injury is multifactorial and polygeneic (many genes interacting) and needs more research to investigate the risk associated with these polymorphisms. Ultimately, these genetic variations could also alter how tendons heal following the injury. Therefore, it would be advantageous to determine if these genetic risk factors can help us implement better individualized rehabilitation programs. Then, we can prescreen athletes for these polymorphisms and tailor the rehab specifically knowing how their tissue healing is affected. Eventually, these genetics studies may lay the foundation for an era when we can identify patients that warrant extra injury prevention procedures or need modified rehabilitation programs. Do you see the same patients with tendonitis in different locations?
Written by: Jane McDevitt MS, ATC, CSCS
Reviewed by: Stephen Thomas