ArticleHaematologica2013
Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin.
Article in Haematologica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00011648 (Determining the Prevalence and Prognosis of Secondary Pulmonary Hypertension in Adult Patients With Sickle Cell Anemia), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Determining the Prevalence and Prognosis of Secondary Pulmonary Hypertension in Adult Patients With Sickle Cell Anemia
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia.Science advances · 2019Trial
- Iron, inflammation, and early death in adults with sickle cell disease.Circulation research · 2015Trial
- Pharmacologic Inhibition of Erythrocyte Ferroportin Expression ExacerbatesMicroorganisms · 2025Article
- Effects of DNA, RNA, and Protein Methylation on the Regulation of Ferroptosis.International journal of biological sciences · 2023Review
- Article
- Molecular mechanisms of hepatic dysfunction in sickle cell disease: lessons from Townes mouse model.American journal of physiology. Cell physiology · 2022Review
- Ferroptosis and Its Emerging Role in Pre-Eclampsia.Antioxidants (Basel, Switzerland) · 2022Review
- Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional Features.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.Science (New York, N.Y.) · 2018Article
- Nuclear transcription factor Nrf2 suppresses prostate cancer cells growth and migration through upregulating ferroportin.Oncotarget · 2016Article
- Ironing out Ferroportin.Cell metabolism · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Ferroportin Q248H mutation has an allele frequency of 2.2-13.4% in African populations and is associated with a mild tendency to increased serum ferritin in the general population. Some investigators have reported that ferroportin Q248H is degraded after exposure to hepcidin in exactly the same manner as wild-type ferroportin, but supraphysiological concentrations of hepcidin were used. The aim of our study was to determine whether ferroportin Q248H may have reduced sensitivity to physiological concentrations of hepcidin. The sensitivity of ferroportin Q248H to hepcidin was determined in 293T cells transiently expressing ferroportin using immunoblotting and fluorescence analysis. Ferritin concentrations were measured in these cells and also in human primary monocytes derived from humans with different ferroportin genotypes. The effect of Q248H on serum iron measures was examined in patients with sickle cell anemia. Immunoblotting and fluorescence analysis showed decreased sensitivity of ferroportin Q248H to physiological concentrations of hepcidin. Lower ferritin concentrations were observed after incubation with iron and hepcidin in 293T cells expressing ferroportin Q248H and in primary monocytes from ferroportin Q248H subjects. In sickle cell anemia, ferroportin Q248H heterozygotes had lower serum ferritin concentrations than wild-type subjects, consistent with enhanced iron release by macrophage ferroportin Q248H. A clinical benefit of ferroportin Q248H was suggested by lower echocardiographic estimates of pulmonary artery pressure in patients carrying mutant alleles. In conclusion, our results suggest that ferroportin Q248H protein is resistant to physiological concentrations of hepcidin and that this mutation has discernible effects on iron metabolism-related clinical complications of sickle cell anemia. They provide a mechanistic explanation for the effect of ferroportin Q248H on iron status in individuals of African descent and suggest that these changes in iron metabolism may be beneficial under certain disease-specific circumstances. (ClinicalTrials.gov Identifier:NCT00011648).
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Registered trials
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.