TY - JOUR
T1 - Dna methylation changes are associated with an incremental ascent to high altitude
AU - Childebayeva, Ainash
AU - Harman, Taylor
AU - Weinstein, Julien
AU - Goodrich, Jaclyn M.
AU - Dolinoy, Dana C.
AU - Day, Trevor A.
AU - Bigham, Abigail W.
AU - Brutsaert, Tom D.
N1 - Publisher Copyright:
© 2019 Childebayeva, Harman, Weinstein, Goodrich, Dolinoy, Day, Bigham and Brutsaert.
PY - 2019
Y1 - 2019
N2 - 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, EPAS1, EPO, PPARa, and RXRa. We found significantly lower DNA methylation between baseline (1,400 m) and high altitudes in LINE-1, EPO (at 4,240 m only), and RXRa. We found increased methylation in EPAS1 (at 4,240 m only) and PPARa. We also found positive associations between EPO methylation and systolic blood pressure and RXRa 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.
AB - 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, EPAS1, EPO, PPARa, and RXRa. We found significantly lower DNA methylation between baseline (1,400 m) and high altitudes in LINE-1, EPO (at 4,240 m only), and RXRa. We found increased methylation in EPAS1 (at 4,240 m only) and PPARa. We also found positive associations between EPO methylation and systolic blood pressure and RXRa 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.
KW - Altitude
KW - DNA methylation
KW - Epigenetics
KW - Hypoxia
KW - Incremental ascent
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U2 - 10.3389/fgene.2019.01062
DO - 10.3389/fgene.2019.01062
M3 - Article
AN - SCOPUS:85074786841
SN - 1664-8021
VL - 10
JO - Frontiers in Genetics
JF - Frontiers in Genetics
IS - OCT
M1 - 1062
ER -