Differential Responses to Concurrent Training in High-Level Football Players According to the ACE I/D (rs4646994) Polymorphism

Background: This exploratory study examined associations between Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (ACE I/D) and aerobic and strength responses to concurrent training in high-level football players. Methods: Twenty-five male players completed six weeks of concurrent training (DD, n = 8; ID, n = 10; II, n = 7). Outcomes were peak oxygen uptake (VO2peak), squat one-repetition maximum (1RM), and bench press 1RM. Primary analyses assessed genotype × time interactions using mixed-design repeated-measures analysis of variance (ANOVA), with Benjamini–Hochberg correction across outcomes and Holm-adjusted pairwise comparisons of changes. Supplementary analyses included baseline-adjusted analysis of covariance (ANCOVA)and change-score regressions adjusted for age and body mass index, with HC3 robust standard errors. Results: All three outcomes improved significantly within each genotype group. Genotype × time interactions were significant for VO2peak, squat 1RM, and bench press 1RM (Benjamini–Hochberg-adjusted p = 0.0015, 0.0015, and 0.0028, respectively). Holm-adjusted comparisons showed greater VO2peak gains in ID and II than in DD (adjusted p ≤ 0.006). DD showed greater squat and bench press gains than ID and II (adjusted p ≤ 0.026). No outcome differed significantly between ID and II after Holm adjustment. However, the ID versus DD difference in VO2peak change was not significant in age- and BMI-adjusted regression with HC3 standard errors (p = 0.063). Conclusions: ACE I/D genotype was associated with differences in aerobic and strength adaptations following concurrent training in this small cohort. Support for individual comparisons varied across analyses. These exploratory findings require replication in larger independent cohorts before genotype-based training prescriptions can be justified.