Genome-Wide DNA Methylation Changes Associated With High-Altitude Acclimatization During an Everest Base Camp Trek

Ainash Childebayeva, Taylor Harman, Julien Weinstein, Trevor Day, Tom D. Brutsaert, Abigail W. Bigham

Research output: Contribution to journalArticlepeer-review

Abstract

The individual physiological response to high-altitude hypoxia involves both genetic and non-genetic factors, including epigenetic modifications. Epigenetic changes in hypoxia factor pathway (HIF) genes are associated with high-altitude acclimatization. However, genome-wide epigenetic changes that are associated with short-term hypoxia exposure remain largely unknown. We collected a series of DNA samples from 15 participants of European ancestry trekking to Everest Base Camp to identify DNA methylation changes associated with incremental altitude ascent. We determined genome-wide DNA methylation levels using the Illumina MethylationEPIC chip comparing two altitudes: baseline 1,400 m (day 0) and elevation 4,240 m (day 7). The results of our epigenome-wide association study revealed 2,873 significant differentially methylated positions (DMPs) and 361 significant differentially methylated regions (DMRs), including significant positions and regions in hypoxia inducible factor (HIF) and the renin–angiotensin system (RAS) pathways. Our pathway enrichment analysis identified 95 significant pathways including regulation of glycolytic process (GO:0006110), regulation of hematopoietic stem cell differentiation (GO:1902036), and regulation of angiogenesis (GO:0045765). Lastly, we identified an association between the ACE gene insertion/deletion (I/D) polymorphism and oxygen saturation, as well as average ACE methylation. These findings shed light on the genes and pathways experiencing the most epigenetic change associated with short-term exposure to hypoxia.

Original languageEnglish (US)
Article number660906
JournalFrontiers in Physiology
Volume12
DOIs
StatePublished - Jun 28 2021

Keywords

  • epigenetics (DNA methylation)
  • genome-wide DNA methylation analysis
  • HIF pathway
  • high altitude acclimatization
  • hypoxia

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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