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ORIGINAL RESEARCH article

Front. Physiol.
Sec. Environmental, Aviation and Space Physiology
Volume 15 - 2024 | doi: 10.3389/fphys.2024.1477070

Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300m

Provisionally accepted
Ruoting Yang Ruoting Yang 1*Aarti Gautam Aarti Gautam 1Rasha Hammamieh Rasha Hammamieh 1Robert C. Roach Robert C. Roach 2Beth A. Beidleman Beth A. Beidleman 3
  • 1 Walter Reed Army Institute of Research, Silver Spring, United States
  • 2 University of Colorado, Denver, Colorado, United States
  • 3 US Army Research Institute of Environmental Medicine (USARIEM), Natick, Massachusetts, United States

The final, formatted version of the article will be published soon.

    Acute mountain sickness (AMS) is a common altitude illness that occurs when individuals rapidly ascend to altitudes ≥ 2,500m without proper acclimatization. Genetic and genomic factors can contribute to the development of AMS or predispose individuals to susceptibility. This study aimed to investigate differential gene regulation and biological pathways to diagnose AMS from high-altitude (HA; 4,300m) blood samples and predict AMS-susceptible (AMS+) and AMS-resistant (AMS─) individuals from sealevel (SL; 50m) blood samples. Two independent cohorts were used to ensure a robust study design and minimize spurious findings. Notable genes, including hemoglobin genes (HBA1, HBA2 and HBB) and Phosphodiesterase 5A (PDE5A), emerged as distinguishing factors between AMS+ and AMS─ individuals at HA. Interestingly, the cAMP response element-binding protein (CREB) pathway exhibited contrasting regulatory patterns before and after ascent, indicative of adaptation to hypoxic conditions at HA. Additionally, putative diagnostic and predictive biomarker panels are proposed. Overall, the identification of a potential transcriptomic signature for AMS holds promise to improve its diagnosis and treatment. These findings provide valuable insights into the underlying biological mechanisms contributing to the development of AMS and may pave the way for targeted and effective therapeutic interventions.

    Keywords: NGS - next generation sequencing, acute mountain sickness, biomarker, machine learning, high altitude

    Received: 07 Aug 2024; Accepted: 20 Dec 2024.

    Copyright: © 2024 Yang, Gautam, Hammamieh, Roach and Beidleman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ruoting Yang, Walter Reed Army Institute of Research, Silver Spring, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.