ArticleClinical epigenetics2022
Differential methylation in EGLN1 associates with blood oxygen saturation and plasma protein levels in high-altitude pulmonary edema.
Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 11 citations in OpenAlex.
- Downregulation of EPAS1 and EGLN1 mRNA Expression Associated With High-Altitude Adaptive Genetic Variants in Sherpa Highlanders.Annals of human genetics · 2026Article
- SARS-CoV-2 altered mitochondrial DNA methylation in Indian COVID-19 patients.Scientific reports · 2026Article
- Rapid-onset respiratory failure following diesel aspiration at 4,200 m: a case report.Frontiers in medicine · 2026Article
- Epigenetic dichotomy in florid vs. gliotic proliferative diabetic retinopathy: hypomethylation of EGLN1 and MMP9 drives divergent pathogenic pathways in angiogenesis and fibrosis.Frontiers in endocrinology · 2026Article
- Research progress on high-altitude hypoxia pulmonary injury: pathogenesis and Chinese herbal medicine for prevention and treatment.Frontiers in pharmacology · 2026Review
- DNA methylation in adaptation to high-altitude environments and pathogenesis of related diseases.Human genomics · 2025Review
- AZU1 as a DNA Methylation-Driven Gene: Promoting Oxidative Stress in High-Altitude Pulmonary Edema.Antioxidants (Basel, Switzerland) · 2025Article
- Advances in Understanding Adaptive Hemoglobin Concentration at High Altitude.American journal of human biology : the official journal of the Human Biology Council · 2025Article
- Dysregulation of metabolites and high-altitude illnesses development under plateau conditions.Frontiers in physiology · 2025Review
- [Research Progress in the Role of Hypoxia-Inducible Factor 1 in Altitude Sickness and the Mechanisms Involved].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- Understanding Hypoxia-Driven Tumorigenesis: The Interplay of HIF1A, DNA Methylation, and Prolyl Hydroxylases in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2024Article
- Hypobaric hypoxia modulated structural characteristics of circulating cell-free DNA in high-altitude pulmonary edema.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Ginsenosides ameliorates high altitude-induced hypoxia injury in lung and kidney tissues by regulating PHD2/HIF-1α/EPO signaling pathway.Frontiers in pharmacology · 2024Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh-altitude (HA, 2500 m) hypoxic exposure evokes a multitude of physiological processes. The hypoxia-sensing genes though influence transcriptional output in disease susceptibility; the exact regulatory mechanisms remain undetermined in high-altitude pulmonary edema (HAPE). Here, we investigated the differential DNA methylation distribution in the two genes encoding the oxygen-sensing HIF-prolyl hydroxylases, prolyl hydroxylase domain protein 2 (PHD2) and factor inhibiting HIF-1α and the consequent contributions to the HAPE pathophysiology.
methodsDeep sequencing of the sodium bisulfite converted DNA segments of the two genes, Egl nine homolog 1 (EGLN1) and Hypoxia Inducible Factor 1 Subunit Alpha Inhibitor (HIF1AN), was conducted to analyze the differential methylation distribution in three study groups, namely HAPE-patients (HAPE-p), HAPE-free sojourners (HAPE-f) and healthy HA natives (HLs). HAPE-p and HAPE-f were permanent residents of low altitude (< 200 m) of North India who traveled to Leh (3500 m), India, and were recruited through Sonam Norboo Memorial (SNM) hospital, Leh. HLs were permanent residents of altitudes at and above 3500 m. In addition to the high resolution, bisulfite converted DNA sequencing, gene expression of EGLN1 and HIF1AN and their plasma protein levels were estimated.
resultsA significantly lower methylation distribution of CpG sites was observed in EGLN1 and higher in HIF1AN (P < 0.01) in HAPE-p compared to the two control groups, HAPE-f and HLs. Of note, differential methylation distribution of a few CpG sites, 231,556,748, 231,556,804, 231,556,881, 231,557,317 and 231,557,329, in EGLN1 were significantly associated with the risk of HAPE (OR = 4.79-10.29; P = 0.048-004). Overall, the methylation percentage in EGLN1 correlated with upregulated plasma PHD2 levels (R = - 0.36, P = 0.002) and decreased peripheral blood oxygen saturation (SpO
conclusionsSignificantly lower methylation distribution in EGLN1 and the consequent physiological influences annotated its functional epigenetic relevance in the HAPE pathophysiology.
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