Global expression profiling and pathway analysis in two different population groups in relation to high altitude.

Area of Science:

• Human physiology
• Genomics
• Altitude medicine

Background:

• High altitude (HA) presents numerous physiological stresses.
• Individual responses to HA stress vary significantly due to factors like ancestry, duration of residency, and ethnicity.
• Understanding these population-specific variations is crucial for interpreting physiological adaptations.

Purpose of the Study:

• To investigate population-specific transcriptome variability in response to high altitude exposure.
• To compare gene expression profiles between Indian and Kyrgyz lowland populations at baseline and after 7 days at 3200m.
• To identify key signaling pathways and molecular mechanisms underlying differential adaptation.

Main Methods:

• Array-based global gene expression profiling of RNA from male volunteers.
• Analysis of gene expression at baseline and on day 7 of HA exposure (3200m).
• Ingenuity Pathway Analysis (IPA) and gene ontology for pathway enrichment.
• Quantitative real-time PCR (qRT-PCR) for validation.

Main Results:

• Significant differences in gene expression between Kyrgyz and Indian populations at baseline and on day 7 of HA exposure.
• Kyrgyz showed marked translational repression at baseline, indicated by downregulated ribosomal proteins and negative eIF2 signaling activation.
• On day 7, Kyrgyz exhibited enriched cAMP-mediated signaling with higher plasma cAMP and extracellular adenosine levels compared to Indians.
• Upregulation of ADORA2B and CD73, with downregulation of ENTs in Kyrgyz, suggests activation of the extracellular cAMP-adenosine pathway.

Conclusions:

• Transcriptome changes at high altitude are population-specific.
• The Kyrgyz population demonstrates unique adaptive mechanisms involving translational regulation and adenosine signaling.
• Extrapolation of HA response data across different populations requires careful consideration of genetic and environmental factors.