Chuvash polycythemia VHLR200W mutation is associated with down-regulation of hepcidin expression
Open accessAbstract
Hypoxia is known to reduce the expression of hepcidin, the master regulator of iron metabolism. However, it is not clear whether this response is primarily related to increased erythropoiesis driven by hypoxically stimulated erythropoietin or to a more direct effect of hypoxia on hepcidin expression. The germline loss-of-function VHL(R200W) mutation is common in Chuvashia, Russia, and also occurs elsewhere. VHL(R200W) homozygotes have elevated hypoxia-inducible factor 1α (HIF-1α) and HIF-2α levels, increased red cell mass, propensity to thrombosis, and early mortality. Ninety VHL(R200W) homozygotes and 52 controls with normal VHL alleles from Chuvashia, Russia, were studied under basal circumstances. In univariate analyses, serum hepcidin concentration was correlated positively with serum ferritin concentration and negatively with homozygosity for VHL(R200W). After adjustment for serum erythropoietin and ferritin concentrations by multiple linear regression, the geometric mean (95% confidence interval of mean) hepcidin concentration was 8.1 (6.3-10.5) ng/mL in VHL(R200W) homozygotes versus 26.9 (18.6-38.0) ng/mL in controls (P < .001). In contrast, a significant independent relationship of serum erythropoietin, hemoglobin, or RBC count with hepcidin was not observed. In conclusion, up-regulation of the hypoxic response leads to decreased expression of hepcidin that may be independent of increased erythropoietin levels and increased RBC counts.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Serum iron and ferritin levels are decreased in Chuvash patients and in individuals sojourning at high altitude for 10-12 days.
“Serum iron and ferritin levels are decreased in Chuvash patients and in individuals sojourning at high altitude for 10–12 days.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [191]
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 [191]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 48 · Cited by 51
- Authors
- Gordeuk, V. R., Miasnikova, G. Y., Sergueeva, A. I., Niu, X., Nouraie, M., Okhotin, D. J., Polyakova, L. A., Ammosova, T., Nekhai, S., Ganz, T., & Prchal, J. T.
- Affiliations
- Howard University (US)
- Chuvash Republic Clinical Hospital No. 1, Cheboksary, Russia;
- Cheboksary Children's Hospital, Cheboksary, Russia;
- Russian Research Services, Camas, WA;
- University of California, Los Angeles (US)
- University of Utah (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-11-10
- Volume
- 118
- Issue
- 19
- Pages
- 5278-5282
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3217409
- OpenAlex
- W2135827580
- Cited by
- 51
- References
- 48
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 1 · 2014: 3 · 2013: 8 · 2012: 5
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Howard (Howard University) (submittedVersion)
- Funders
- National Institutes of Health (5r01hl079912-04)
- National Heart, Lung, and Blood Institute (R01HL079912-01, UH1-HL03679-05, R01-HL079912, R01HL50077-14, UH1HL003679, R01HL050077)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065029)
- National Center for Research Resources (MO1 RR10284, M01RR010284)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- hepcidin, hypoxia, iron metabolism, hypoxia-inducible factor-1α, HIF-2α, erythropoietin, serum ferritin, Chuvash polycythemia, erythrocytosis
- MeSH terms
- Adult, Erythropoietin, Female, Ferritins, Homozygote, Humans, Male, Middle Aged, Polycythemia, Russia, Down-Regulation, Case-Control Studies, Germ-Line Mutation, Antimicrobial Cationic Peptides, Von Hippel-Lindau Tumor Suppressor Protein, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
