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

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.

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DNA Methylation Explains a Subset of Placental Gene Expression Differences Based on Ancestry and Altitude

10.1101/261974 ◽

2018 ◽

Author(s):

William E. Gundling ◽

Priyadarshini Pantham ◽

Nicholas P Illsley ◽

Lourdes Echalar ◽

Stacy Zamudio ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Birth Weight ◽

Native Americans ◽

High Altitude ◽

Mrna Expression ◽

European Ancestry ◽

Gene Body Methylation ◽

Genome Wide ◽

Or Gene

Abstract:Objectives: The most pronounced effect of high altitude (>2700m) on reproductive outcomes is reduced birth weight. Indigenous Bolivians (Andean Native Americans) residing for generations at high altitudes have higher birth weights relative to more recent migrants of primarily European ancestry. Previous research demonstrated that the placenta is a key contributor to the preservation of Andean birth weight at high altitude. Our current research investigated how gene expression and epigenetics contributes to the conservation of birth weight at high altitude by examining mRNA expression and DNA methylation differences between placentas of Andeans and those of European ancestry residing at high and low altitude.Methods: Genome-wide mRNA expression and DNA methylation of villous placenta tissue was quantified utilizing microarray technology. Subjects were of Andean and European ancestry and resident at high (3600m) or low (400m) altitudes. Differentially expressed genes (DEGs) associated with altitude or ancestry were identified (FDR<0.1, |fold change|>1.25). To predict which DEGs could be regulated by methylation we tested for correlation between gene expression and methylation values.Results: 69 DEGs associated with altitude (n=36) or ancestry (n=34) were identified. Altitude-associated DEGs included members of the AP-1 transcription factor family. Ancestry-associated DEGs were implicated in inflammatory pathways and associated with pro-angiogenic macrophages. More ancestry-associated DEGs correlated significantly (n=17) (FDR<0.1) with promoter or gene body methylation (p=0.0242) when compared to altitude associated DEGs (n=8).Conclusions:Compared to altitude-associated DEGs, methylation regulates more ancestry-associated DEGs, potentially allowing for rapid modification in the expression of inflammatory genes to attract pro-angiogenic macrophages as a means of promoting placental capillary growth in Andeans, regardless of altitude.

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The influence of short-term high-altitude acclimatization on cerebral and leg tissue oxygenation post-orthostasis

European Journal of Applied Physiology ◽

10.1007/s00421-021-04765-7 ◽

2021 ◽

Author(s):

Masahiro Horiuchi ◽

Kazunobu Okazaki ◽

Katsumi Asano ◽

Alexander T. Friend ◽

Gabriella M. K. Rossetti ◽

...

Keyword(s):

High Altitude ◽

Tissue Oxygenation ◽

Short Term ◽

Altitude Acclimatization ◽

High Altitude Acclimatization

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Short-Term Effects on Gene-Expression and on DNA-Methylation at the Genome-Wide Level of the Iberian Ham Intake and Compared With Orange Intake: A Crossover Randomized Trial

Current Developments in Nutrition ◽

10.1093/cdn/nzab050_004 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 937-937

Author(s):

Dolores Corella ◽

José Sorlí ◽

Eva Asensio ◽

Rocío Barragán ◽

Olga Portolés ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Randomized Trial ◽

Intervention Group ◽

Enrichment Analysis ◽

Differentially Expressed ◽

European Ancestry ◽

Pathway Enrichment Analysis ◽

Short Term ◽

Genome Wide

Abstract Objectives Diet regulates gene expression and methylation profiles by several mechanisms. However, studies analyzing the simultaneous effect of specific foods on gene-expression and DNA methylation at the genome-wide level are very scarce. Therefore our aims were: To study the short-term transcriptomics and epigenomcis effects at the genome-wide level of the Iberian ham intake compared with orange intake in the same subjects. Methods We carried out a cross-over randomized trial (registered at ISRCTN17906849) in 33 healhty volunteers (aged 18–50 years and 50% females) of European ancestry. After 12h fasting, participants were randomly allocated to eat 67.5 g of Iberian ham (100% pure iberian breed and 100% acorn fed) or 500 g of peeled oranges (Citrus reticulata) depening on the intervention group. After a washout period, subjects were crossed over to the alternate treatment arm. Blood samples were taken at 0-h and at 4-h to isolate DNA and RNA from leukocytes. A random sample of 16 participants was selected for omics analyses (gene expression with the. GeneChip Human Gene 2.0 ST Array, and the EPIC-Illumina array (850K) for methylation). Eight arrays (2 times and 2 treatments per 2 omics) were obtained for each participant. Differences in gene expression and methylation (4 h vs baseline) were analyzed for Iberian ham, oranges and combined. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Results The top-ranked genes differentially expressed P < 1 × 10–5) after Iberian ham intake (4 h vs baseline) were PKBP5 and PICALM. Pantothenate and CoA biosyntesis and the JAK-STAT singaling pathways were the most significantly enriched (P < 5 × 10–7). After orange intake, the top-ranked differentially expressed genes (P < 5 × 10–6) were: SMAP2 and RHEB, the pathways being (P < 5 × 10–9): Cellular senescence and ABC transporters. We detected top-ranked methylated CpGs both for ham and oranges, resulting the Chemokine signaling pathway differentially methylated for oranges and in the Neurothrophine singaling pathway for Iberian ham intake. Comparative combined analysis revealed additional differences. Conclusions A short-term intake of Iberian ham or oranges results in differences in gene expression as well as in DNA-methylation. Funding Sources CIBEROBN-06/03/035, PROMETEO-17/2017 APOSTD/2019/136), P1–1B2013–54 and COGRUP/2016/06

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Energy and nutrient intakes during high-altitude acclimatization

Journal of Wilderness Medicine ◽

10.1580/0953-9859-5.3.318 ◽

1994 ◽

Vol 5 (3) ◽

pp. 318-324

Author(s):

C.E. Fenn

Keyword(s):

High Altitude ◽

Nutrient Intakes ◽

Altitude Acclimatization ◽

High Altitude Acclimatization

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Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men

Diabetologia ◽

10.1007/s00125-012-2717-8 ◽

2012 ◽

Vol 55 (12) ◽

pp. 3341-3349 ◽

Cited By ~ 124

Author(s):

S. C. Jacobsen ◽

C. Brøns ◽

J. Bork-Jensen ◽

R. Ribel-Madsen ◽

B. Yang ◽

...

Keyword(s):

Skeletal Muscle ◽

Dna Methylation ◽

Young Men ◽

High Fat ◽

Short Term ◽

Genome Wide

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Impact of depression and stress on placental DNA methylation in ethnically diverse pregnant women

Epigenomics ◽

10.2217/epi-2021-0192 ◽

2021 ◽

Author(s):

Markos Tesfaye ◽

Suvo Chatterjee ◽

Xuehuo Zeng ◽

Paule Joseph ◽

Fasil Tekola-Ayele

Keyword(s):

Dna Methylation ◽

Fetal Brain ◽

Ethnically Diverse ◽

Antenatal Depression ◽

Epigenetic Changes ◽

Clinical Trial Registration ◽

False Discovery ◽

Genome Wide ◽

Neuropsychiatric Diseases ◽

Registration Number

Aim: To investigate the association between placental genome-wide methylation at birth and antenatal depression and stress during pregnancy. Methods: We examined the association between placental genome-wide DNA methylation (n = 301) and maternal depression and stress assessed at six gestation periods during pregnancy. Correlation between DNA methylation at the significantly associated CpGs and expression of nearby genes in the placenta was tested. Results: Depression and stress were associated with methylation of 16 CpGs and two CpGs, respectively, at a 5% false discovery rate. Methylation levels at two of the CpGs associated with depression were significantly associated with expression of ADAM23 and CTDP1, genes implicated in neurodevelopment and neuropsychiatric diseases. Conclusion: Placental epigenetic changes linked to antenatal depression suggest potential fetal brain programming. Clinical trial registration number: NCT00912132 (ClinicalTrials.gov)

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