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Cited by 275Erythropoietin and Anemia TreatmentCancer, Hypoxia, and MetabolismHemoglobinopathies and Related Disorders

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

Congenital disorder of oxygen sensing: association of the homozygous Chuvash polycythemia VHL mutation with thrombosis and vascular abnormalities but not tumors

Gordeuk, Victor R., Sergueeva, Adelina I., Miasnikova, Galina Y., Okhotin, Daniel, Voloshin, Yaroslav, Choyke, Peter L., Butman, John A., Jedlickova, Katerina, Prchal, Josef T., Polyakova, Lydia A.·2004·Blood
DOI 10.1182/blood-2003-07-2535
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Abstract

Adaptation to hypoxia is critical for survival and regulates multiple processes, including erythropoiesis and vasculogenesis. Chuvash polycythemia is a hypoxia-sensing disorder characterized by homozygous mutation (598C>T) of von Hippel-Lindau gene (VHL), a negative regulator of hypoxia sensing. Although endemic to the Chuvash population of Russia, this mutation occurs worldwide and originates from a single ancient event. That VHL 598C>T homozygosity causes elevated normoxic levels of the transcription factor hypoxia inducible factor-1α (HIF-1α), serum erythropoietin and hemoglobin is known, but the disease phenotype has not been documented in a controlled manner. In this matched cohort study, VHL 598C>T homozygosity was associated with vertebral hemangiomas, varicose veins, lower blood pressures, and elevated serum vascular endothelial growth factor (VEGF) concentrations (P < .0005), as well as premature mortality related to cerebral vascular events and peripheral thrombosis. Spinocerebellar hemangioblastomas, renal carcinomas, and pheochromocytomas typical of classical VHL syndrome were not found, suggesting that overexpression of HIF-1α and VEGF is not sufficient for tumorigenesis. Although hemoglobin-adjusted serum erythropoietin concentrations were approximately 10-fold higher in VHL 598C>T homozygotes than in controls, erythropoietin response to hypoxia was identical. Thus, Chuvash polycythemia is a distinct VHL syndrome manifested by thrombosis, vascular abnormalities, and intact hypoxic regulation despite increased basal expression of hypoxia-regulated genes.

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Research works printed but not linked: 1

  1. Jaakola P, Mole DR, Tian YM, et al. Targeting of HIF-alpha to the von Hippel Lindau ubiqutiylation complex by O2-regulated hydroxylation. Science. 2001;292: 48-72.

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Metadata

Authors
Gordeuk, V. R., Sergueeva, A. I., Miasnikova, G. Y., Okhotin, D., Voloshin, Y., Choyke, P. L., Butman, J. A., Jedlickova, K., Prchal, J. T., & Polyakova, L. A.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2004-05-15
Volume
103
Issue
10
Pages
3924-3932
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2003-07-2535
OpenAlex
W1979891446
Cited by
273
References
43
Citations by year
2026: 4 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 18 · 2021: 13 · 2020: 10 · 2019: 10 · 2018: 9 · 2017: 9 · 2016: 15 · 2015: 13 · 2014: 6 · 2013: 14 · 2012: 15
FWCI
11.33
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Howard (Howard University) (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL5007-09, UH1-HL03679-05, UH1HL003679, R01HL066333, R01HL66333-01)
  • National Center for Research Resources (M01RR010284, M01-RR10284)
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 (clinical) › Hemoglobinopathies and Related Disorders
Keywords
Chuvash polycythemia, von Hippel-Lindau gene, hypoxia sensing, HIF-1α, erythropoietin, thrombosis, vertebral hemangioma, varicose veins, vascular endothelial growth factor, hypoxia adaptation, von Hippel-Lindau disease
MeSH terms
Adaptation, Physiological, Adolescent, Adult, Hypoxia, Child, Cross-Sectional Studies, Female, Homozygote, Humans, Male, Mutation, Neoplasms, Polycythemia, Retrospective Studies, Russia, Syndrome, Thrombosis, Transcription Factors, Vascular Diseases, Survival Rate, Tumor Suppressor Proteins, Vascular Endothelial Growth Factor A, Ubiquitin-Protein Ligases, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit

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