Genetic determinants of tendon and ligament injuries in athletes: a narrative review from single variants to gene-gene interactions

Tendon and ligament injuries are common in athletes and can result in significant functional impairment. Genetic factors are increasingly recognized as key contributors to individual susceptibility. A structured narrative literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar to identify studies investigating genetic polymorphisms associated with tendon and ligament injuries in athletic populations. Eligible studies published in English and involving elite, professional, recreational, or physically active individuals were narratively synthesized. This review synthesizes current evidence on polymorphisms associated with these injuries, identifying 70 genes and 107 variants across candidate-gene studies, haplotype analyses, and genome-wide association studies (GWAS). Specifically, the evidence included 33 candidate genes with 43 polymorphisms, 25 polymorphisms evaluated in haplotype analyses involving these candidate genes as well as three additional genes, and 34 genes identified through GWAS encompassing 39 variants. These genes are involved in extracellular matrix (ECM) organization, inflammation, tissue remodeling, angiogenesis, and muscle function. Structural genes, particularly collagens ( COL1A1, COL3A1, COL5A1 ), proteoglycans ( ACAN, DCN, BGN ), matrix remodeling ( MMPs, TIMP2 ), and glycoproteins ( FMOD, TNC ), as well as genes related to inflammatory ( IL1B, IL6, TNF- α), and vascular pathways ( VEGFA, VEGFR2) , were frequently implicated. Importantly, gene-gene interactions and haplotypes appear to be more informative than single polymorphisms for explaining injury risk. Although GWAS studies remain limited, they have identified novel loci, reinforcing the polygenic nature of these conditions. Overall, these findings highlight the complexity of genetic influences and support integrating genetic, biomechanical, and environmental factors to improve personalized prevention and rehabilitation strategies in sports medicine.