The Role of COL1A1, COL5A1, ACTN3, MMP3, and GDF5 Gene Variants in Common Sports Injuries: Systematic Review of ACL Rupture, Achilles Tendinopathy, and Stress Fractures.

BACKGROUND

Anterior cruciate ligament (ACL) rupture, Achilles tendinopathy, and stress fracture are common sports injuries with significant long-term effects on performance and health. Despite similar exposure, injury susceptibility varies among athletes, suggesting a genetic component. Variants in COL1A1, COL5A1, ACTN3, MMP3, and GDF5 genes influence collagen integrity, muscle performance, and extracellular matrix remodelling, making them potential risk factors.

OBJECTIVE

To systematically review associations between five selected genes and musculoskeletal injury risk.

METHODS

Following PRISMA 2020 guidelines, PubMed, EMBASE, SPORTDiscus, and Web of Science were searched for studies examining these genes in relation to sports injuries. Data were extracted using Covidence and assessed for quality via the Newcastle-Ottawa Scale (NOS).

RESULTS

Twenty-six studies (n > 7000) were included. COL1A1 rs1800012 showed a protective effect against ACL rupture; COL5A1 rs1272 and rs13946 increased risk for ACL rupture and Achilles tendinopathy. MMP3 variants (rs679620, 5A/6A) showed variable associations, particularly in combination with COL5A1. ACTN3 R577X was linked to higher muscle and soft tissue injury risk in XX genotype carriers. Evidence for GDF5 rs143383 was limited but suggested a possible association with stress fractures.

CONCLUSIONS

Genetic variants in COL1A1, COL5A1, MMP3, ACTN3, and GDF5 may influence susceptibility to ACL rupture, Achilles tendinopathy, and stress fractures. Larger, multi-ethnic studies are needed to validate these findings and inform personalised injury prevention strategies.