Genomics: Insight

Societal Implications of Tendon Injury:

Tendinopathy and tendon rupture are both very common injuries, accounting for about 1 in 2 sports injuries and 1 in 3 visits to general practitioners in the overall population.⁵ The most common people to suffer from these injuries are athletes who utilize repeating and high-stress motions, like running, baseball, and tennis, with about 50% of all sports injuries being tendinopathy or a tendon rupture.4 Though tendon injuries are never fatal and rarely permanent, they can still come with severe immediate, and relatively long-term impacts. Because the athlete is unable to perform in their sport for weeks, if not several months, they can lose money, practice, and even a promising future career.  While injuries may seem random and inevitable, injuries relating to overuse are somewhat predictable when a combination of genetic markers and environmental factors is assessed. Based on a series of studies surrounding Single Nucleotide Polymorphisms (SNPs), which are variations in single nucleotides within DNA, in specific genes and how each polymorphism affects one’s chances of suffering from a tendon injury, it is possible to predict how at-risk an athlete is of injuring themselves in such a way. It is not by any means a perfect system, and the predictors can only foresee potential injuries in ethnic groups that initially participated in the study. But when the right prerequisites are met for this system, it has a chance of impacting an athlete’s well-being and future career dramatically.

This paper will be reviewing three genetic markers and one environmental factor that contribute to a greater risk of tendon injury and determining the relative significance of the different types of factors.

Using Genomic Markers & Environmental Factors to Predict Tendon Injury Risk:

TNC

The Tenascin-C (TNC) gene is responsible for carrying the information to produce the TNC glycoprotein, which assists in cell adhesion, signaling, proliferation, and migration. Mokone et. al. conducted a study involving 114 recreational South African athletes, 72 of whom suffered from tendinopathy, and 42 of whom suffered from tendon rupture, vs 127 controls, and the study focused on revealing the connection between alleles (i.e. trait-causing variations of genes) and tendon injury. They found a large presence of the repetition of the 12 or 14 GT dinucleotide and a lack of repetition of the 13 or 17 allele (P < 0.001 in both cases) within the South African patient population.1

TIMP2

The TIMP2 gene contains instructions to produce the TIMP metallopeptidase enzyme inhibitor that suppresses the proliferation of differentiated cells as well as MMPs that break down extracellular matrices. El Khoury et. al.’s study, focusing on white British participants and the association of SNPs and tendon injury, contained 118 patients suffering from Achilles tendon injury, of which 93 had tendinopathy and 25 had full tendon rupture, and 131 controls. They discovered a correlation between a TIMP2 SNP and Achilles tendon injury, with a P value of P = 0.38, and a larger presence of the CC genotype (P = 0.012) in patients rather than controls.1

CoL11A1

The COL11A1 gene is responsible for encoding the chain of type XI Collagen, which is responsible for protecting the spacing and diameter of articular cartilage. Hay et. al, attempting to discover a connection between haplotypes, combinations of alleles from one chromosome, and tendon injury, conducted their study using South African and Australian participants in a study with 184 Achilles tendinopathy patients and 338 controls. Their study uncovered that the TCT(AGGG) variant had a significantly greater presence within the patient population, with 25% of patients vs 9.1% of controls containing the variant (P = 0.003).1 

BMI

While there are a multitude of genetic factors associated with the risk of tendinopathy, it is important to note that environmental factors have a much more significant association with tendinopathy than genetic factors. Environmental factors like Body Fat Percentage and BMI, stemming from the nutritional and caloric value of food consumed, returned a much more significant correlation than any genetic marker. They found that the correlation between BMI and elbow tendon pathology possessed a P value of 0.00002. Percent body fat returned a P value of 0.00003, weight returned a P value of 0.001, and waist circumference returned a P value of 0.003. These predictors, especially BMI, had significantly higher correlations with elbow tendon pathology than any genetic factor studied and should be considered primary predictors of elbow tendinopathy.3

Environmental factors… returned a much more significant correlation than any genetic marker.

Relative Predictive Value of Genetic and Environmental Factors:

There is no singular flawless predictor of an athlete’s risk of tendinopathy, but there are several genetic and environmental factors that act as predictors for certain sections of people, depending on the depth of data relating to their ethnicity. Genetic factors have proven to contain relative importance to the prediction. There are several aforementioned SNPs that demonstrate a statistically significant relationship between a given genetic difference and a greater likelihood of tendon injury, though each variation affects the risk of tendon injury only very slightly. However, it is equally, if not more, important to consider environmental factors such as Body Mass Index, and daily level of activity. Both of these extrinsic factors stress and weaken the tendons in different ways than genetic factors do, and ultimately have a greater impact on the health of tendons, as they damage the tendon health directly rather than decreasing the strength from the beginning. While it is critical to assess every factor while attempting to predict the risk of tendon injury in a patient, as every factor contributes, no matter how little, certain factors, like the ones based on environment, are fundamentally more important to the determination of tendon injury risk, and therefore must be assessed with greater urgency than genetic factors.

Reflection:

Tendon injury is the single most common injury in athletes, and thus is the most critical to understand to create a comprehensive library of knowledge and a functional predictive model that accurately assesses risk. To accomplish this, it is important to consider not only the combination and balance between genetic and environmental factors but also the ethnic groups that the studies consider. While it would be difficult to systematically and algorithmically classify and identify an athlete’s risk of tendon injury, utilizing such a predictive model is a far better method of saving athletes from suffering career-ending injuries than merely attempting to repair the tendon once it’s damaged. Ultimately, the topic of tendon injury is deeply important to society as it is, but it is particularly critical regarding those whose future depends on the security of their athletic career.

It is important to consider… the ethnic groups that the studies involve.

Bibliography

1. Vaughn N, Stepanyan H, Gallo R, Dhawan A. (2017). Genetic Factors in Tendon Injury: A Systematic Review of Literature. PubMed Central. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549180/
2. Ribbans W, September A, Collins M. (2022). Tendon and Ligament Genetics: How Do They Contribute to Disease and Injury? A Narrative Review.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147569/
3. Mohmara Y, Cook J, Benítez-Martínez J, McPeek E, Aguilar A, Olivas E, Hernandez-Sanchez S. (2020). Influence of genetic factors in elbow tendon pathology: a case-control study. https://www.nature.com/articles/s41598-020-63030-7
4. Berkay F, Minhus A, Krishnamurthy A, Lyons J. (2023). Poster 375: Incidence of Tendon Ruptures in the US: Comparison of Differences Across Racial Groups. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10392274/ 
5. Kaux JF, Forthomme B, Goff CL, Crielaard JM, Croisier JL. Current opinions on tendinopathy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761855/