Distinct temporal trajectories of EPAS1 mRNA expression during moderate-altitude training in Han and Tibetan...

EPAS1 encodes hypoxia-inducible factor-2α and is strongly implicated in high-altitude adaptation, but its longitudinal transcriptional response during altitude training remains poorly understood. This study examined temporal changes in EPAS1 mRNA expression during moderate-altitude training in Han and Tibetan endurance athletes.

Han (n = 16) and Tibetan (n = 17) male endurance athletes completed 4 weeks of naturalistic training at approximately 2,260 m. Han athletes ascended from low altitude, whereas Tibetan athletes descended from habitual residence and training environments above 3,500 m. EPAS1 mRNA expression was measured longitudinally, and whole-blood lncRNA and mRNA profiles were examined exploratorily in a subset of seven athletes per cohort.

EPAS1 expression showed a significant group-by-time interaction (p < 0.001). In Han athletes, expression was 21.5% lower at Week 1 than at Baseline (expression ratio 0.785, 95% CI 0.681-0.906) and did not differ detectably from Baseline at Week 4 (0.997, 95% CI 0.864-1.150). In Tibetan athletes, expression was 28.5% higher at Week 1 (1.285, 95% CI 1.152-1.434) and remained 22.6% higher at Week 4 (1.226, 95% CI 1.099-1.368). No significant changes were detected in the measured hematological variables. Exploratory transcriptomic analysis showed differential expression by Week 1 in Han athletes and later-emerging whole-blood transcriptional changes in Tibetan athletes; no Gene Ontology Biological Process terms survived FDR correction.

Han and Tibetan endurance athletes showed distinct temporal patterns of EPAS1 mRNA expression during moderate-altitude training. These longitudinal findings provide a basis for further investigation of their physiological significance.