The ACTN3 R577X Nonsense Allele Is Underrepresented in Professional Volleyball Players and Associated with an Increased Risk of Muscle Injury in Female Players

Cerit, M, Tuncer, SY, Piri, MM, Anılır, M, John, G, Semenova, EA ORCID: 0000-0003-1248-2855, Larin, AK ORCID: 0000-0002-9429-792X, Generozov, EV ORCID: 0000-0002-6314-4883, Ahmetov, II ORCID: 0000-0002-6335-4020, Ulucan, K and Szabo, A ORCID: 0000-0003-2788-4304 (2025) The ACTN3 R577X Nonsense Allele Is Underrepresented in Professional Volleyball Players and Associated with an Increased Risk of Muscle Injury in Female Players. Genes, 16 (9).

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Abstract

Background: Muscle injuries pose a significant challenge in sports, leading to decreased performance and shortened career longevity. Individuals homozygous for the nonsense X allele of the ACTN3 rs1815739 (R577X) polymorphism, characterized by a complete absence of α-actinin-3, have been associated with reduced power performance and may have an increased injury risk. This study aimed to investigate the association between the ACTN3 R577X polymorphism and both volleyball player status and the risk of non-contact musculoskeletal injuries in female volleyball players. Methods: The study included 5382 Turkish and Russian subjects of European descent (187 professional volleyball players and 5195 controls), of whom 50 female players provided injury data. Sport-related injury information was obtained from medical records maintained by team physicians and physiotherapists. Results: A pooled analysis of the two cohorts demonstrated that the frequency of the ACTN3 X allele was significantly lower in volleyball players than in controls, with an odds ratio of 0.763 (95% CI: 0.61–0.95, p = 0.02). In the pre-specified recessive contrast (XX vs. RR + RX) among 50 players, exact methods indicated higher injury odds for the XX genotype (OR = 7.87, 95% CI: 0.94–374.58; p = 0.0366), which was classified as borderline/exploratory. Penalized (Firth) regression produced estimates of a similar magnitude after adjustment for age and playing position (adjusted OR = 5.92, 95% CI: 1.12–60.98), although confidence intervals remained wide. Conclusions: The ACTN3 X allele is underrepresented in professional volleyball players, and it is associated with an increased risk of muscle injury in female players.

Item Type:	Article
Uncontrolled Keywords:	0604 Genetics; 3105 Genetics
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport and Exercise Sciences
Publisher:	MDPI
Date of acceptance:	12 September 2025
Date of first compliant Open Access:	22 September 2025
Date Deposited:	22 Sep 2025 10:10
Last Modified:	22 Sep 2025 10:15
DOI or ID number:	10.3390/genes16091076
URI:	https://researchonline.ljmu.ac.uk/id/eprint/27188

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