Global expression profiling and pathway analysis in two different population groups in relation to high altitude
High altitude (HA) is associated with number of stresses. Response of these stresses may vary in different populations depending upon altitude, duration of residency, ancestry, geographical variation, lifestyle, and ethnicities. For understanding population variability in transcriptome, array-based global gene expression profiling was performed on extracted RNA of male volunteers of two different lowland population groups, i.e., Indians and Kyrgyz, at baseline and day 7 of HA exposure (3200 m). A total of 97 genes were differentially expressed at basal in Kyrgyz as compared to Indians (82 downregulated and 15 upregulated), and 196 were differentially expressed on day 7 of HA (118 downregulated and 78 upregulated). Ingenuity Pathway Analysis and gene ontology highlighted eIF2 signaling with most significant negative activation z score at basal in Kyrgyz compared to Indians with downregulation of various L- and S-ribosomal proteins indicating marked translational repression. On day 7, cAMP-mediated signaling is most enriched with positive activation z score in Kyrgyz compared to Indians. Plasma cAMP levels were higher in Kyrgyz on day 7 compared to Indians. Extracellular adenosine levels were elevated in both the groups upon HA, but higher in Kyrgyz compared to Indians. Valedictory qRT-PCR showed upregulation of ADORA2B and CD73 along with downregulation of ENTs in Kyrgyz compared to Indians indicating elevated levels of extracellular nucleotides mainly adenosine and activation of extracellular cAMP-adenosine pathway which as per literature triggers endogenous protective mechanisms under stress conditions like hypoxia. Thus, transcriptome changes at HA are population-specific, and it may be necessary to take care while interposing similar results in different populations.
KeywordsHypoxia High altitude Adenosine Acclimatization
The authors are grateful to the troops of the Indian and Kyrgyz Army for volunteering to participate in the study. We express our gratitude to DGAFMS and SD branch for their support. We also acknowledge Mr. Karan Pal and Mr. Alpesh Kumar Sharma of our lab for their valuable support in the study.
PV was involved in the study concept, design, data acquisition, and drafting of the manuscript. SS wrote the paper and was involved in data acquisition, interpretation, analysis, and drafting the work for important intellectual content. SB, PG, KR, KK, MS, AA, and AM were involved in data acquisition and coordination of study process. BK was involved in drafting and revising the work for important intellectual content. AS and SBS have set up the study concept and design and were responsible for drafting of the manuscript, supervision, and coordination of study process. All the authors approved the final version of the manuscript.
The work is funded by the Defence Institute of Physiology and Allied Sciences (DIPAS), Defence R&D Organization (DRDO).
Compliance with ethical standards
The study conformed to the Ethical guidelines of the institute and in accordance with Helsinki declaration.
The authors declare that they have no conflict of interest.
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