Evidence map›Paper›PMID 41655047›Full record

ArticleAnnals of human genetics2026

Downregulation of EPAS1 and EGLN1 mRNA Expression Associated With High-Altitude Adaptive Genetic Variants in Sherpa Highlanders.

Yunden Droma, Fengming Yue, Masao Ota, Nobumitsu Kobayashi, Yoshiaki Kitaguchi, Masayuki Hanaoka

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of human genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Yunden DromaFirst Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Fengming YueDepartment of Histology and Embryology, Shinshu University School of Medicine, Matsumoto, Japan.
Masao OtaDepartment of Medicine, Division of Hepatology and Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan.
Nobumitsu KobayashiFirst Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Yoshiaki KitaguchiFirst Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Masayuki HanaokaFirst Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

Funding

Japan Society for the Promotion of Science
6 · The paper itself

Abstract

BACKGROUND AND

aimsSherpa highlanders exhibit remarkable tolerance to hypoxia, most likely due to genetic adaptations shaped by natural selection at high altitude. This study examined the roles of endothelial PAS domain protein 1 (EPAS1) and egl-9 family hypoxia-inducible factor 1 (EGLN1) in the genetic mechanisms underlying this adaptation.

methodsBlood samples were collected from 56 Sherpa highlanders residing in Namche Bazaar (3440 m) and 25 non-Sherpa lowlanders in Kathmandu (1300 m). Samples were measured for serum erythropoietin (EPO) concentrations, genetic variants of EPAS1 (rs13419896:G>A; rs4953354:A>G) and EGLN1 (rs1435166:G>A; rs2153364:A>G), and mRNA expression levels of the EPAS1 and EGLN1.

resultsOxygen saturation (SpO

conclusionHigh-altitude adaptive genetic variants in EPAS1 and EGLN1 are associated with reduced systemic mRNA expression of these genes and a blunted EPO response in Sherpa highlanders, suggesting transcriptional modulation of the hypoxia-induced factor pathway under chronic hypoxia. This attenuated hypoxic response manifests as the tolerance to hypoxia in Sherpa highlanders, enabling Sherpas to adapt to high-altitude hypoxia.

Indexed as

Adaptation, PhysiologicalAltitudeBasic Helix-Loop-Helix ProteinsHypoxia-Inducible Factor-Proline DioxygenasesDown-RegulationEndothelial PAS Domain-Containing Protein 1ErythropoietinHumansMaleNepalPolymorphism, Single NucleotideRNA, MessengerBasic Helix-Loop-Helix ProteinsEGLN1 protein, humanEndothelial PAS Domain-Containing Protein 1EPO protein, humanErythropoietinHypoxia-Inducible Factor-Proline DioxygenasesRNA, MessengerEGLN1EPAS1erythropoietinhigh‐altitude adaptationhypoxia toleranceSherpa highlanders

Identifiers

PMID41655047
PMCPMC13040315

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.