Tendinopathies in lower extremities (legs)

The probability of suffering tendinopathy in the lower extremities, in addition to being affected by a multitude of environmental factors such as exercise, is also affected by the genetic component. Variants in the genes that regulate the development and maintenance of bones, cartilage and tendons play a fundamental role in the predisposition of certain people to suffer injuries.

Tendons are anatomical structures located between the muscle and the bone, whose function is to transmit the force generated by the muscle to the bone, giving rise to joint movement. They are composed mostly of collagen (30%) and water (68%), with a small proportion of elastin (2%). The amount of blood vessels in them is scarce, but increases during exercise and healing processes.

One of the main characteristics associated with the tendon is its ability to recover and return to its normal state after damage or injury. To this end, it is important to know the individual, genetic, biomechanical and environmental factors that interact with each other and that make it possible to prevent and optimize recovery from tendinopathies. Tendinopathies" are a group of pathologies that affect the tendons and which, according to the International Rheumatology Association, are classified into two large groups: inflammatory and non-inflammatory.

The most frequent lesions in the tendons of the lower extremities are:

  • Achilles tendinopathy: The Achilles tendon is the largest and strongest tendon in the entire body, connects the triceps suralis to the heel, performs plantar flexion of the foot and participates in knee flexion. Associated risk factors are usually overuse, repetitive trauma, vascular disease, genetic predisposition, neuropathies and rheumatologic diseases that can cause tendon degeneration.
  • Quadriceps tendon injury: The quadriceps femoris is a large, powerful muscle located in the front of the thigh. The muscles and tendons that comprise it form contractile units that stabilize the hip and knee and allow their movement. Injuries to the quadriceps muscles and tendons are common among athletes and active adults.
  • Cruciate ligament rupture: The cruciate ligaments are two structures that cross inside the knee, joining the tibia to the femur and providing stability in extension and flexion movements. The anterior cruciate ligament prevents the tibia from moving forward with respect to the femur and its rupture is the most frequent. On the other hand, the posterior cruciate ligament prevents the tibia from moving backwards. The injury of these ligaments is produced after a sudden change of direction of the knee, an exaggerated deceleration or a contusion.

Several studies have identified 7 markers associated with the risk of tendinopathies and ligament ruptures in the lower extremities. These markers are mainly found in genes such as COL1A1, COL5A1, GDF5, TIMP2, TNC, ADAMTS14 and MMP3. These genes are involved in the maintenance, development and repair of bone, cartilage and other soft musculoskeletal tissues, such as tendons and ligaments.

Type I collagen is the major protein that makes up tendons and ligaments. It is composed of chains or fibrils encoded by the COL1A1 and COL1A2 genes. It is known that mutations in the COL1A1 gene can cause connective tissue diseases such as osteogenesis imperfecta or Ehlers-Danlos syndrome, as well as other less dramatic tendon and ligament disorders that may be related to athletic performance. The ADAMTS14 gene produces an enzyme involved in the process of collagen synthesis.

GDF5 encodes for a growth factor that is essential for bone and cartilage development.

The MMP3 protein is responsible for degrading components of the extracellular matrix of tissues and is part of the metalloproteinase family. Therefore, variants in the MMP3 gene can affect the breakdown of soft tissues such as tendons and ligaments. The TIMP2 gene produces a small protein that binds to metalloproteinases and inhibits their functions.

The TNC (tenascin-C) gene encodes a protein involved in cell adhesion to the matrix. Genetic variants in TNC can affect the elasticity conferred by tenascin-C to tissues, thereby affecting wound healing and tissue remodeling.

Number of observed variants

13.5 million variants

Number of variants analyzed in the study

7 variants


El Khoury L, Ribbans WJ, Raleigh SM. MMP3 and TIMP2 gene variants as predisposing factors for Achilles tendon pathologies: Attempted replication study in a British case-control cohort. Meta gene, 2016; 9:52–5.

Posthumus M, September A V, Schwellnus MP, Collins M. Investigation of the Sp1-binding site polymorphism within the COL1A1 gene in participants with Achilles tendon injuries and controls. J Sci Med Sport, 2009; 12(1):184–9.

St?pie?-S?odkowska M, Ficek K, Kaczmarczyk M, Maciejewska-Kar?owska A, Sawczuk M, Leo?ska-Duniec A, et al. The Variants Within the COL5A1 Gene are Associated with Reduced Risk of Anterior Cruciate Ligament Injury in Skiers. J Hum Kinet, 2015; 45(1):103–11.

Vaughn NH, Stepanyan H, Gallo RA, Dhawan A. Genetic Factors in Tendon Injury: A Systematic Review of the Literature. Orthop J Sport Med, 2017; 5(8):232596711772441.

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