Tendon and Ligament Genetics: How Do They Contribute to Disease and Injury? A Narrative Review

Abstract

A significant proportion of patients requiring musculoskeletal management present with tendon and ligament pathology. Our understanding of the intrinsic and extrinsic mechanisms that lead to such disabilities is increasing. However, the complexity underpinning these interactive multifactorial elements is still not fully characterised. Evidence highlighting the genetic components, either reducing or increasing susceptibility to injury, is increasing. This review examines the present understanding of the role genetic variations contribute to tendon and ligament injury risk. It examines the different elements of tendon and ligament structure and considers our knowledge of genetic influence on form, function, ability to withstand load, and undertake repair or regeneration. The role of epigenetic factors in modifying gene expression in these structures is also explored. It considers the challenges to interpreting present knowledge, the requirements, and likely pathways for future research, and whether such information has reached the point of clinical utility.

Are commercial genetic injury tests premature?

“…As previously mentioned, musculoskeletal injuries are multifactorial and genetic factors together with numerous nongenetic factors modulate risk of injury. 1 Any future tests need to be injury specific, and companies should specify the genetic markers they use so that the scientific community can independently evaluate the scientific evidence. Potential markers should be independently verified in all population groups using well defined clinical and other criteria to define both the cases and controls.…”

“…1 Several rheumatological, endocrine, and metabolic disorders, which in their own right, have an inherited component, can also modulate the risk of injuries. 1 A heritability of 42% and 40% has been estimated for frozen shoulder and tennis elbow, respectively 10 , and as high as 69% for anterior cruciate ligament (ACL) rupture. 11 In fact, most of the intrinsic risk factors for musculoskeletal tissue injuries are also multifactorial, with a genetic contribution.…”

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The evidence suggesting that there is a genetic component to multifactorial musculoskeletal tissue injuries such as tendons, ligaments, bone, and other tissues is growing. 1 In parallel, several direct-to-consumer (DTC) genetic testing companies have emerged around the world that claim to be able to test for susceptibility to exercise-associated injury. A total of 39 companies were previously mentioned to market DTC genetic tests related to sport and exercise performance or sports injury, 21 appeared to no longer exist and 12 did not appear to offer DTC tests for sports

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Functional biomaterials for tendon/ligament repair and regeneration

“…Although technology has advanced in recent years, the issue of rehabilitation of tendon injuries has not met everyone’s expectations and remains a serious clinical challenge [ 11 ]. The conservative clinical approach uses fixed casts and restricted movement orthoses, which require a long ongoing rehabilitation program to achieve functional recovery [ 12 ].…”

The Association of Variants within Types V and XI Collagen Genes with Knee Joint Laxity Measurements

“…Furthermore, it was previously proposed that COL5A1 , which encodes the α(1) chain of type V collagen, is associated with hypermobility spectrum disorders [ 4 ] and, although joint hypermobility is not a clinical feature, multifocal fibromuscular dysplasia (FMDMF) [ 5 ]. Common genetic variants within the COL5A1 gene are also associated with several musculoskeletal soft tissue injuries [ 6 ], including anterior cruciate ligament (ACL) ruptures and other ligament injuries [ 7 ]. Interestingly, increased generalised joint hypermobility (GJH) and knee joint laxity are also intrinsic risk factors for ACL rupture [ 8 ].…”