ACE I/D AND ACTN3 R577X POLYMORPHISMS IN SKELETAL MUSCLE RECOVERY AND HYPERTROPHIC ADAPTATION DURING POST-OPERATIVE REHABILITATION: A NARRATIVE REVIEW

Abstract

Background: Skeletal muscle loss and impaired muscle function are common consequences of surgery, particularly when recovery involves immobilisation, pain, reduced physical activity, and prolonged limited mechanical loading. Progressive rehabilitation can substantially restore muscle strength and mass, yet individuals often respond differently to apparently similar rehabilitation programmes. Genetic variation has therefore attracted interest as one possible contributor to inter individual differences in muscular adaptation. Among the most extensively investigated variants are the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the α-actinin-3 (ACTN3) R577X polymorphism. Objective: This narrative review examines the potential relevance of ACE I/D and ACTN3 R577X polymorphisms to skeletal muscle recovery, strength restoration, muscle damage, and hypertrophic adaptation during postoperative rehabilitation. Methods: Relevant literature examining ACE and ACTN3 polymorphisms, skeletal muscle phenotypes, resistance training adaptations, exercise-induced muscle damage, immobilisation, and postoperative rehabilitation was considered. Particular emphasis was placed on systematic reviews, meta-analyses, longitudinal resistance-training studies, and mechanistic investigations. Results: The available evidence suggests that ACE and ACTN3 are biologically relevant to skeletal muscle phenotypes, but their effects are neither large nor sufficiently consistent to support their use as independent predictors of postoperative recovery. ACTN3 R577X is associated with the expression of α-actinin-3 in fast skeletal muscle fibres, and recent meta analytic evidence indicates associations with selected measures of maximal strength, maximal voluntary contraction, and jumping performance. However, findings concerning hypertrophic responses to resistance training have been inconsistent. Similarly, ACE I/D has been associated with physical-performance phenotypes in some populations, but studies of resistance training have not consistently demonstrated genotype-dependent differences in muscle hypertrophy. Evidence regarding ACTN3 and exercise-induced muscle damage is also mixed, with stronger indications of genotype-related effects during prolonged, high-volume endurance exercise than during resistance exercise. Conclusion: ACE I/D and ACTN3 R577X may contribute to individual variation in skeletal muscle characteristics and exercise adaptation, but current evidence is insufficient to establish either polymorphism as a determinant of postoperative muscle recovery or hypertrophy. Future research should investigate these variants prospectively in surgical populations while simultaneously accounting for rehabilitation dose, age, sex, nutritional status, baseline muscle characteristics, adherence, and surgical factors. Genotype-guided rehabilitation remains a promising research concept rather than an established clinical practice.