Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 m
IntroductionAcute mountain sickness (AMS) is a common altitude illness that occurs when individuals rapidly ascend to altitudes ≥2,500 m without proper acclimatization. Genetic and genomic factors can contribute to the development of AMS or predispose individuals to susceptibility. This study aimed...
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Frontiers Media S.A.
2025-01-01
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| author | Ruoting Yang Aarti Gautam Rasha Hammamieh Robert C. Roach Beth A. Beidleman |
| author_facet | Ruoting Yang Aarti Gautam Rasha Hammamieh Robert C. Roach Beth A. Beidleman |
| author_sort | Ruoting Yang |
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| description | IntroductionAcute mountain sickness (AMS) is a common altitude illness that occurs when individuals rapidly ascend to altitudes ≥2,500 m 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; 4,300 m) blood samples and predict AMS-susceptible (AMS+) and AMS-resistant (AMS─) individuals from sea-level (SL; 50 m) blood samples.MethodsTwo independent cohorts were used to ensure the robustness of the findings. Blood samples were collected from participants at SL and HA. RNA sequencing was employed to profile gene expression. Differential expression analysis and pathway enrichment were performed to uncover transcriptomic signatures associated with AMS. Biomarker panels were developed for diagnostic and predictive purposes.ResultsAt HA, hemoglobin-related genes (HBA1, HBA2, and HBB) and phosphodiesterase 5A (PDE5A) emerged as key differentiators between AMS+ and AMS− individuals. The cAMP response element-binding protein (CREB) pathway exhibited contrasting regulatory patterns at SL and HA, reflecting potential adaptation mechanisms to hypoxic conditions. Diagnostic and predictive biomarker panels were proposed based on the identified transcriptomic signatures, demonstrating strong potential for distinguishing AMS+ from AMS− individuals.DiscussionThe findings highlight the importance of hemoglobin-related genes and the CREB pathway in AMS susceptibility and adaptation to hypoxia. The differential regulation of these pathways provides novel insights into the biological mechanisms underlying AMS. The proposed biomarker panels offer promising avenues for the early diagnosis and prediction of AMS risk, which could enhance preventive and therapeutic strategies. |
| format | Article |
| id | doaj-art-0adb6795ef76442bba0ef44879714e8a |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj-art-0adb6795ef76442bba0ef44879714e8a2025-01-29T06:45:46ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-01-011510.3389/fphys.2024.14770701477070Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 mRuoting Yang0Aarti Gautam1Rasha Hammamieh2Robert C. Roach3Beth A. Beidleman4Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD, United StatesMedical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD, United StatesMedical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD, United StatesAltitude Research Center, University of Colorado Anschutz Medical Center, Aurora, CO, United StatesMilitary Performance Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United StatesIntroductionAcute mountain sickness (AMS) is a common altitude illness that occurs when individuals rapidly ascend to altitudes ≥2,500 m 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; 4,300 m) blood samples and predict AMS-susceptible (AMS+) and AMS-resistant (AMS─) individuals from sea-level (SL; 50 m) blood samples.MethodsTwo independent cohorts were used to ensure the robustness of the findings. Blood samples were collected from participants at SL and HA. RNA sequencing was employed to profile gene expression. Differential expression analysis and pathway enrichment were performed to uncover transcriptomic signatures associated with AMS. Biomarker panels were developed for diagnostic and predictive purposes.ResultsAt HA, hemoglobin-related genes (HBA1, HBA2, and HBB) and phosphodiesterase 5A (PDE5A) emerged as key differentiators between AMS+ and AMS− individuals. The cAMP response element-binding protein (CREB) pathway exhibited contrasting regulatory patterns at SL and HA, reflecting potential adaptation mechanisms to hypoxic conditions. Diagnostic and predictive biomarker panels were proposed based on the identified transcriptomic signatures, demonstrating strong potential for distinguishing AMS+ from AMS− individuals.DiscussionThe findings highlight the importance of hemoglobin-related genes and the CREB pathway in AMS susceptibility and adaptation to hypoxia. The differential regulation of these pathways provides novel insights into the biological mechanisms underlying AMS. The proposed biomarker panels offer promising avenues for the early diagnosis and prediction of AMS risk, which could enhance preventive and therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fphys.2024.1477070/fullNGS - next generation sequencingacute mountain sicknessbiomarkermachine learninghigh altitude |
| spellingShingle | Ruoting Yang Aarti Gautam Rasha Hammamieh Robert C. Roach Beth A. Beidleman Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 m Frontiers in Physiology NGS - next generation sequencing acute mountain sickness biomarker machine learning high altitude |
| title | Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 m |
| title_full | Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 m |
| title_fullStr | Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 m |
| title_full_unstemmed | Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 m |
| title_short | Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 m |
| title_sort | transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4 300 m |
| topic | NGS - next generation sequencing acute mountain sickness biomarker machine learning high altitude |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2024.1477070/full |
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