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ACTN3 c.1729C>T Polymorphism Might Not Be a Standalone Factor in Non-contact Musculoskeletal Injury: A Systematic
David Varillas-Delgado1,2, Estela Villaoslada3, Laura Clavaín3
1Research Unit, Faculty of Health Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain. david.varillas@ufv.es.
Sports Medicine (Auckland, N.Z.)
|November 26, 2025
Summary
The ACTN3 gene's c.1729C>T polymorphism is not consistently linked to non-contact musculoskeletal injury incidence. However, the TT genotype may increase injury severity, particularly under a recessive model, warranting cautious interpretation and further research.
Area of Science:
- Genetics and Sports Medicine
- Molecular Biology and Exercise Science
Background:
- The association between the ACTN3 gene c.1729C>T polymorphism and non-contact musculoskeletal injuries is debated.
- Existing research shows discrepancies and a lack of consensus regarding this genetic link.
Purpose of the Study:
- To systematically review and meta-analyze the influence of ACTN3 gene c.1729C>T polymorphism on non-contact musculoskeletal injury incidence and severity.
- To investigate potential differences based on athlete sex and sport discipline.
Main Methods:
- Comprehensive literature search across PubMed, Embase, SPORTDiscus, and Web of Science.
- Inclusion of longitudinal and cross-sectional studies assessing injury rates and severity.
- Risk of bias assessment using the Newcastle-Ottawa Scale and meta-analysis using RevMan 5.4.1.
Main Results:
- A significant association was found between CT and TT genotypes and injury severity (OR 0.39; p=0.008).
- The TT genotype, under a recessive model, showed a significantly higher risk of non-contact musculoskeletal injuries (OR 2.55; p=0.01).
- No significant associations were identified for injury incidence, sex bias, or sport modality across other models.
Conclusions:
- No consistent evidence supports the ACTN3 gene's association with non-contact musculoskeletal injury incidence.
- The TT genotype may be linked to increased injury severity, but findings require cautious interpretation due to study heterogeneity.
- Further research with standardized methods and larger cohorts is needed to clarify ACTN3's role in injury risk and severity.
