GENETIC PREDISPOSITION TO SPORTS-RELATED MUSCULOSKELETAL INJURIES: A SYSTEMATIC REVIEW

Abstract

Sports-related musculoskeletal injuries (SRMSIs) arise from interacting intrinsic and extrinsic risk factors, and growing evidence suggests that genetic polymorphisms may influence susceptibility, injury severity, and recovery. This systematic review synthesized evidence on genetic variants associated with SRMSIs. We searched PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library for observational studies published from 2018 to 2026 that evaluated candidate-gene polymorphisms or genome-wide associations in athletes or physically active individuals. Study characteristics, participant profiles, injury outcomes, genetic variants, and principal findings were extracted and synthesized narratively according to biological function. Sixteen studies involving more than 4,000 athletes and physically active individuals were included. Most studies involved elite football players and non-contact muscle injuries. ACTN3 R577X showed the most consistent association with injury susceptibility; the XX genotype was linked to greater injury risk (odds ratios 2.0-7.87), higher injury frequency, longer return-to-play times, and poorer performance. Associations involving ACE varied across populations. Variants in COL1A1, COL5A1, MMP3, IL6, NOS3, HIF1A, and VDR were associated with muscle, connective-tissue, hamstring, or stress-fracture outcomes, while recent genome-wide association studies identified novel loci including PAPPA2, MAS1, and the intergenic region between OR10G7 and VWA5A. Genetic susceptibility to SRMSIs appears to involve multiple biological pathways, including muscle function, extracellular-matrix integrity, inflammation, vascular regulation, and bone metabolism. ACTN3 currently has the strongest evidence, but larger multicenter studies and external validation are required before genetic profiling can be incorporated into routine injury-risk assessment or athlete management.