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Cited by 510Erythropoietin and Anemia TreatmentCancer, Hypoxia, and MetabolismHemoglobinopathies and Related Disorders

Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia

Ang, Sonny O., Chen, Hua, Hirota, Kiichi, Gordeuk, Victor R., Jelinek, Jaroslav, Guan, Yongli, Liu, Enli, Sergueeva, Adelina I. +6 more·2002·Nature Genetics
DOI 10.1038/ng1019
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Abstract

Chuvash polycythemia is an autosomal recessive disorder that is endemic to the mid-Volga River region. We previously mapped the locus associated with Chuvash polycythemia to chromosome 3p25. The gene associated with von Hippel-Lindau syndrome, VHL, maps to this region, and homozygosity with respect to a C-->T missense mutation in VHL, causing an arginine-to-tryptophan change at amino-acid residue 200 (Arg200Trp), was identified in all individuals affected with Chuvash polycythemia. The protein VHL modulates the ubiquitination and subsequent destruction of hypoxia-inducible factor 1, subunit alpha (HIF1alpha). Our data indicate that the Arg200Trp substitution impairs the interaction of VHL with HIF1alpha, reducing the rate of degradation of HIF1alpha and resulting in increased expression of downstream target genes including EPO (encoding erythropoietin), SLC2A1 (also known as GLUT1, encoding solute carrier family 2 (facilitated glucose transporter), member 1), TF (encoding transferrin), TFRC (encoding transferrin receptor (p90, CD71)) and VEGF (encoding vascular endothelial growth factor).

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Crossref · 10.1038/ng1019

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36 of 36 references verified0 citation errors · 0 not checkable

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  • Chuvash polycythemia is caused by a homozygous mutation in VHL at codon 200, R200W.

    “It is caused by a homozygous mutation in the VHL tumor suppressor at codon 200, R200W”

    From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [126]

  • Experimental studies in cultured cells, animal models and human subjects have established that hepcidin production is O2-sensitive and involves the HIF pathway.

    “Experimental studies in cultured cells, in animal models and in human subjects have established that hepcidin production is O2-sensitive and involves the HIF pathway.”

    From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [126]

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Authors
Ang, S. O., Chen, H., Hirota, K., Gordeuk, V. R., Jelinek, J., Guan, Y., Liu, E., Sergueeva, A. I., Miasnikova, G. Y., Mole, D., Maxwell, P. H., Stockton, D. W., Semenza, G. L., & Prchal, J. T.
Affiliations
  • Baylor College of Medicine (US)
  • Johns Hopkins University (US)
  • Howard University (US)
  • Chuvash State University (RU)
  • University of Oxford (GB)
Corresponding author
Prchal, Josef T.
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2002-11-04
Volume
32
Issue
4
Pages
614-621
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng1019
OpenAlex
W2135034560
Cited by
510
References
36
Citations by year
2026: 12 · 2025: 10 · 2024: 16 · 2023: 13 · 2022: 14 · 2021: 17 · 2020: 22 · 2019: 15 · 2018: 13 · 2017: 13 · 2016: 21 · 2015: 25 · 2014: 20 · 2013: 33 · 2012: 19
FWCI
10.96
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Howard (Howard University) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Keywords
Chuvash polycythemia, VHL gene, von Hippel-Lindau disease, oxygen homeostasis, hypoxia-inducible factor, erythropoietin, transferrin receptor, GLUT1, vascular endothelial growth factor, autosomal recessive disorder, chromosome 3p25, protein-protein interaction
MeSH terms
Adolescent, Adult, Alleles, Cells, Cultured, Chromosomes, Human, Pair 3, DNA-Binding Proteins, Erythropoietin, Female, Gene Expression Regulation, Gene Frequency, Haplotypes, von Hippel-Lindau Disease, Homeostasis, Homozygote, Humans, Ligases, Male, Nuclear Proteins, Oxygen, Pedigree, Polycythemia, Protein Binding, Receptors, Transferrin, Russia, Transcription Factors, Transferrin, Tumor Cells, Cultured, Ubiquitins, Germ-Line Mutation, Amino Acid Substitution, Mutation, Missense, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Hypoxia-Inducible Factor 1, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit

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