Hypoxic training enhances endurance sports tolerance. However, individual responses vary due to physiological differences. This study investigated the relationship between genetic factors and exercise tolerance in hypoxic conditions. This randomized crossover study included 22 male university students (age 20.8±1.3 years, peak oxygen uptake 54.5±6.5 mL/min/kg). Incremental load tests were conducted to assess the symptomatic limit on separate days under normoxic and hypoxic conditions (oxygen concentration 15.4±0.8%) using an ergometer. The initial test environment was randomized. The peak oxygen uptake and blood lactate were monitored every minute, and Δ peak oxygen uptake (peak oxygen uptake under hypoxia - peak oxygen uptake under normoxia) was calculated. Sixteen genotypes linked to exercise tolerance (such as angiotensin-converting enzyme [ACE]) were examined. Peak oxygen uptake significantly decreased under hypoxia (p<0.01). Δ peak oxygen uptake varied among individuals (minimum: 0.7 and maximum: - 18.9). Among analyzed genetic polymorphisms, ACE-II genotypes showed significantly greater Δ peak oxygen uptake than ACE-ID/ACE-DD genotypes (p=0.02). ACE-II genotypes exhibited lower blood lactate elevation at peak exercise in normoxic (p=0.01) and hypoxic (p=0.03) conditions. Participants with the ACE-II genotype had lower lactate concentrations and greater reductions in peak oxygen uptake under hypoxic conditions. Optimizing hypoxic training requires individualized programs incorporating genetic analysis.
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