AUTHOR=Childebayeva Ainash , Harman Taylor , Weinstein Julien , Goodrich Jaclyn M. , Dolinoy Dana C. , Day Trevor A. , Bigham Abigail W. , Brutsaert Tom D. 

TITLE=DNA Methylation Changes Are Associated With an Incremental Ascent to High Altitude

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01062

DOI=10.3389/fgene.2019.01062

ISSN=1664-8021

ABSTRACT=<p>Genetic and nongenetic factors are involved in the individual ability to physiologically acclimatize to high-altitude hypoxia through processes that include increased heart rate and ventilation. High-altitude acclimatization is thought to have a genetic component, yet it is unclear if other factors, such as epigenetic gene regulation, are involved in acclimatization to high-altitude hypoxia in nonacclimatized individuals. We collected saliva samples from a group of healthy adults of European ancestry (n = 21) in Kathmandu (1,400 m; baseline) and three altitudes during a trek to the Everest Base Camp: Namche (3,440 m; day 3), Pheriche (4,240 m; day 7), and Gorak Shep (5,160 m; day 10). We used quantitative bisulfite pyrosequencing to determine changes in DNA methylation, a well-studied epigenetic marker, in LINE-1, <italic>EPAS1</italic>, <italic>EPO</italic>, <italic>PPARa</italic>, and <italic>RXRa</italic>. We found significantly lower DNA methylation between baseline (1,400 m) and high altitudes in LINE-1, <italic>EPO</italic> (at 4,240 m only), and <italic>RXRa</italic>. We found increased methylation in <italic>EPAS1</italic> (at 4,240 m only) and <italic>PPARa</italic>. We also found positive associations between <italic>EPO</italic> methylation and systolic blood pressure and <italic>RXRa</italic> methylation and hemoglobin. Our results show that incremental exposure to hypoxia can affect the epigenome. Changes to the epigenome, in turn, could underlie the process of altitude acclimatization.</p>