ArticleAmerican journal of human genetics2007
Common variants in the BMP2, BMP4, and HJV genes of the hepcidin regulation pathway modulate HFE hemochromatosis penetrance.
Article in American journal of human genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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.
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.
Who cites it
45 citing papers in PubMed, 135 citations in OpenAlex.
- Genetic factors associated with iron storage in Australian blood donors.Blood transfusion = Trasfusione del sangue · 2018Trial
- Genetic and lifestyle modifiers of haemochromatosis-related clinical outcomes in HFE C282Y homozygotes.JHEP reports : innovation in hepatology · 2026Article
- Isolated Non-Progressive Hemidystonia in a Patient Homozygous for H63D Variant of Hereditary Hemochromatosis: A Case Report and Systematic Literature Review of Movement Disorders in Hereditary Hemochromatosis.Diagnostics (Basel, Switzerland) · 2025Article
- In defence of ferroptosis.Signal transduction and targeted therapy · 2025Review
- Recurrent BMP4 variants in exon 4 cause non-HFE-associated hemochromatosis via the BMP/SMAD signaling pathway.Orphanet journal of rare diseases · 2024Article
- Genetic variants in HFE are associated with non-alcoholic fatty liver disease in lean individuals.JHEP reports : innovation in hepatology · 2023Article
- Article
- Ethnic Differences in Iron Status.Advances in nutrition (Bethesda, Md.) · 2021Review
- The Proteomics Study of Compounded HFE/TF/TfR2/HJV Genetic Variations in a Thai Family with Iron Overload, Chronic Anemia, and Motor Neuron Disorder.Journal of molecular neuroscience : MN · 2021Article
- Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia.PloS one · 2021Article
- Genetic Variations in the Transforming Growth Factor-β1 Pathway May Improve Predictive Power for Overall Survival in Non-small Cell Lung Cancer.Frontiers in oncology · 2021Article
- Endothelial Bone Morphogenetic Protein 2 (Bmp2) Knockout Exacerbates Hemochromatosis in Homeostatic Iron Regulator (Hfe) Knockout Mice but not Bmp6 Knockout Mice.Hepatology (Baltimore, Md.) · 2020Article
- Article
- Liver iron sensing and body iron homeostasis.Blood · 2019Review
- Iron as a Therapeutic Target inPharmaceuticals (Basel, Switzerland) · 2018Review
- Nomograms incorporating genetic variants in BMP/Smad4/Hamp pathway to predict disease outcomes after definitive radiotherapy for non-small cell lung cancer.Cancer medicine · 2018Article
- Inherited Disorders of Iron Overload.Frontiers in nutrition · 2018Review
- Article
- Bone morphogenetic protein 2 controls iron homeostasis in mice independent of Bmp6.American journal of hematology · 2017Article
- Pathophysiological consequences and benefits ofHaematologica · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most cases of genetic hemochromatosis (GH) are associated with the HFE C282Y/C282Y (p.Cys282Tyr/p.Cys282Tyr) genotype in white populations. The symptoms expressed by C282Y homozygotes are extremely variable. Only a few suffer from an overt disease. Several studies have suggested that, in addition to environmental factors, a genetic component could explain a substantial part of this phenotypic variation, although very few genetic factors have been identified so far. In the present study, we tested the association between common variants in candidate genes and hemochromatosis penetrance, in a large sample of C282Y homozygotes, using pretherapeutic serum ferritin level as marker of hemochromatosis penetrance. We focused on two biologically relevant gene categories: genes involved in non-HFE GH (TFR2, HAMP, and SLC40A1) and genes involved in the regulation of hepcidin expression, including genes from the bone morphogenetic protein (BMP) regulatory pathway (BMP2, BMP4, HJV, SMAD1, SMAD4, and SMAD5) and the IL6 gene from the inflammation-mediated regulation pathway. A significant association was detected between serum ferritin level and rs235756, a common single-nucleotide polymorphism (SNP) in the BMP2 genic region (P=4.42x10-5). Mean ferritin level, adjusted for age and sex, is 655 ng/ml among TT genotypes, 516 ng/ml in TC genotypes, and 349 ng/ml in CC genotypes. Our results further suggest an interactive effect on serum ferritin level of rs235756 in BMP2 and a SNP in HJV, with a small additive effect of a SNP in BMP4. This first reported association between common variants in the BMP pathway and iron burden suggests that full expression of HFE hemochromatosis is linked to abnormal liver expression of hepcidin, not only through impairment in the HFE function but also through functional modulation in the BMP pathway. Our results also highlight the BMP regulation pathway as a good candidate for identification of new modifier genes.
Indexed as
Identifiers
What OpenQuestion holds
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.