Genetic and Molecular Insights into Telomere Biology and Oxidative Stress in High-Altitude Pulmonary Edema

Telomeres protect chromosome ends and support genomic stability through interactions among telomerase, shelterin proteins, DNA-repair factors, and chromatin regulators. Hypobaric hypoxia can induce oxidative stress, DNA damage, and transcriptional changes that may affect telomere maintenance. High-altitude pulmonary edema (HAPE) is characterized by pulmonary vascular dysfunction and increased permeability, but the contribution of telomere biology to HAPE susceptibility remains uncertain. This review summarizes evidence concerning telomere-associated genes, genetic variation, oxidative stress, and hypoxia-responsive pathways, distinguishing direct HAPE findings from evidence derived from other diseases or experimental models. We also outline genomic, transcriptomic, epigenetic, and systems-biology approaches that could test these proposed relationships. Current HAPE omics research has emphasized inflammatory, vascular, metabolic, and hypoxia-responsive pathways; telomere-associated signatures remain insufficiently characterized. We propose a testable framework in which inherited and regulatory variation may modify the relationship between hypoxia-associated oxidative DNA damage, telomere maintenance, and vascular responses. Longitudinal human studies and functional experiments are needed to establish whether telomere alterations precede HAPE, modify disease severity, or arise as a consequence of acute stress.