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Updated: Jun 1, 2026
08:45
Quantitating Iron Transport Across the Mouse Placenta In Vivo Using Nonradioactive Iron Isotopes
Published on: May 10, 2022
Contribution of different HFE genotypes to iron overload disease: a pooled analysis
W Burke1, G Imperatore, S M McDonnell
1Department of Medical History and Ethics, University of Washington, Seattle, Washington 98195, USA. wburke@u.washington.edu.
Summary
Hereditary hemochromatosis risk is highest with C282Y homozygosity in the HFE gene. Other mutations like H63D also increase iron overload risk, suggesting genetic and environmental modifiers influence disease expression.
Area of Science:
- Genetics
- Molecular Biology
- Medical Research
Background:
- Hereditary hemochromatosis is a genetic disorder characterized by excessive iron absorption.
- The HFE gene plays a crucial role in iron metabolism regulation.
- Specific mutations in the HFE gene, C282Y and H63D, are known to be associated with the disease.
Purpose of the Study:
- To quantify the contribution of C282Y and H63D mutations in the HFE gene to the clinical manifestation of hereditary hemochromatosis.
- To evaluate the association between various HFE genotypes and iron overload.
- To estimate the penetrance of the C282Y/C282Y genotype.
Main Methods:
- A pooled analysis of 14 case-control studies involving HFE genotype data.
- Evaluation of the association between different HFE genotypes and iron overload.
- Estimation of C282Y/C282Y genotype penetrance using pooled and published data.
Main Results:
- Homozygosity for the C282Y mutation showed the highest risk for iron overload (OR = 4383) and accounted for most cases (AF = 0.73).
- Other genotypes had smaller risks: C282Y/H63D (OR = 32), H63D/H63D (OR = 5.7), C282Y heterozygosity (OR = 4.1, uncertain association), and H63D heterozygosity (OR = 1.6).
- Penetrance of the C282Y/C282Y genotype was estimated to be unlikely to exceed 50% at a disease prevalence of 2.5 per 1000 or less; penetrance for other genotypes is lower.
Conclusions:
- C282Y homozygosity confers the highest risk for iron overload, but H63D mutations also increase risk.
- A gradient of risk exists across different HFE genotypes, indicating the influence of other genetic or environmental modifiers on hereditary hemochromatosis expression.
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