Genome-Wide DNA Methylation Changes Associated With High-Altitude Acclimatization During an Everest Base Camp Trek
| Autor: | Ainash Childebayeva, Taylor Harman, Julien Weinstein, Trevor Day, Tom D. Brutsaert, Abigail W. Bigham |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Physiology epigenetics (DNA methylation) Biology high altitude acclimatization 03 medical and health sciences 0302 clinical medicine Physiology (medical) medicine QP1-981 Epigenetics Gene Genetics hypoxia Hematopoietic stem cell differentiation Methylation Brief Research Report Hypoxia (medical) HIF pathway 030104 developmental biology Differentially methylated regions Hypoxia-inducible factors DNA methylation medicine.symptom genome-wide DNA methylation analysis 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in Physiology Frontiers in Physiology, Vol 12 (2021) |
| ISSN: | 1664-042X |
| DOI: | 10.3389/fphys.2021.660906 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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