ACE I/D AND NOS3 G894T POLYMORPHISMS AND CARDIOVASCULAR ADAPTATION PROFILES IN ADOLESCENT FOOTBALL PLAYERS.

AIM: To assess the associations of ACE I/D (rs4646994) and NOS3 G894T (rs1799983) polymorphisms with cardiovascular adaptation profiles, autonomic regulation, exercise tolerance and responsiveness to individualized training-load correction in adolescent football players. MATERIALS AND METHODS: This controlled comparative study with an observational pre-post follow-up component included 228 male adolescents aged 13-17 years: 168 football players with at least two years of regular training and 60 non-athlete peers. The examination included anthropometry, body composition assessment, resting and exercise electrocardiography, echocardiography, short-term heart rate variability (HRV) analysis, submaximal bicycle ergometry with PWC170 and estimated VO2max, heart-rate recovery (HRR), and genotyping of ACE I/D and NOS3 G894T polymorphisms. The 3-month individualized training-load correction was analyzed as a non-randomized observational component; therefore, its results were interpreted as post-correction dynamics rather than as definitive evidence of causal efficacy. RESULTS: Football players had a lower resting heart rate than controls (58.6±6.8 vs 72.4±7.5 beats/min; p<0.001), higher PWC170 (196±32.6 vs 142±28.4 W; p<0.001), higher relative PWC170 (3.42±0.52 vs 2.40±0.46 W/kg; p<0.001), higher estimated VO2max (54.0±4.8 vs 42.5±5.2 ml/kg/min; p<0.001) and faster HRR1 (43.6±11.3 vs 25.3±10.4 beats/min; p<0.001). ACE and NOS3 genotype distributions were comparable between football players and controls. Within the athletic cohort, ACE DD and, to a lesser extent, NOS3 T-allele carriage were associated with lower SDNN, RMSSD and pNN50, higher LF/HF and less favorable diastolic indices. After three months of individualized training-load correction, positive HRV and diastolic dynamics were observed mainly in favorable and intermediate genetic profiles, whereas the unfavorable profile showed limited changes. CONCLUSION: ACE I/D and NOS3 G894T polymorphisms should not be interpreted as markers of football participation or selection. They may be considered exploratory modifiers of autonomic reserve, diastolic adaptation and response to individualized training-load monitoring. Integration of genotyping with ECG, echocardiography, HRV, HRR and PWC170 appears promising for personalized monitoring in adolescent football players but requires further external validation. The results of the dynamic stage should be interpreted as observational, since the training-load correction was not randomized.