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Resilience to stress integrates cognitive, physiological, and behavioral adaptations to sustain performance under adversity. Genetic variation in catechol-O-methyltransferase (<i>COMT</i>, rs4680) and angiotensin-converting enzyme (<i>ACE</i>, rs1799752) modulates dopaminergic and renin-angiotensin signaling, influencing tissue oxygenation and fatigue resistance. We examined <i>COMT</i>- and <i>ACE</i>-promoter methylation and genotypes in relation to resilience traits in Swiss tactical athletes (24.6 years) with a maximal power output of 534 W and 21,656 W, respectively, during cardiopulmonary exercise and elbow strike testing. At a 5% false-discovery rate, <i>COMT</i> genotype/methylation explained ~12% of the variance in cognitive performance and metabolic resilience, while <i>ACE</i> explained ~6-7% in strength-endurance and muscle resistance. Antidromic linear associations between <i>COMT</i> genotype and methylation with visual reaction time under reactive stress indicate opposing regulatory influences, best captured by regression models incorporating (epi)genetic covariates. The strongest methylation effects involved <i>COMT</i> promoter associations with muscle hemoglobin content across cardiopulmonary exercise zones (r = 0.43-0.58) and sport-specific strain (r = -0.46). <i>COMT</i>- and <i>ACE</i>-promoter methylation, correlated with time spent in the first aerobic training zone (r = 0.55 and 0.32), indicating environmentally responsive epigenetic modulation. These findings highlight neurovascular-metabolic coupling via dopaminergic and renin-angiotensin pathways as a key mechanism in stress adaptation. System-level adaptations in these pathways align with <i>COMT</i> and <i>ACE</i> (epi)genetic blood profiles, positioning them as candidate resilience biomarkers. Larger, preregistered studies with site-specific CpG analyses and mechanistic assays are needed to establish causal relevance and translational utility for resilience-informed performance optimization in high-stakes professionals.
Published in: International Journal of Molecular Sciences
Volume 27, Issue 3, pp. 1340-1340
DOI: 10.3390/ijms27031340