| Title: | Dietary heme iron intake and common hemochromatosis HFE polymorphisms have similar associations with brain MRI phenotypes: a UK Biobank cohort study |
| Journal: | Journal of Nutrition |
| Published: | 13 Oct 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42869229/ |
| DOI: | https://doi.org/10.1016/j.tjnut.2026.101890 |
Publication 21543
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Abstract
BACKGROUND: Brain iron accumulation is associated with aging and neurodegeneration, but how individual genetics and dietary iron intake affect brain iron is not well understood. Hemochromatosis is a genetic disorder arising from single nucleotide polymorphisms (SNPs) in the HFE gene, causing iron overload and brain iron accumulation, and is associated with accelerated brain aging.</p>
OBJECTIVE: This cross-sectional study examined how dietary iron intake and hemochromatosis-associated single nucleotide polymorphisms are associated with brain MRI phenotypes sensitive to iron.</p>
METHODS: We used a subset of the UK Biobank (N=24,223 participants) to investigate associations between dietary heme and non-heme iron intake (dietary predictors), HFE SNPs rs1799945 and rs1800562 (genetic predictors), brain quantitative susceptibility mapping (QSM) and T2* MRI phenotypes (primary outcomes) using multiple regression. We also investigated associations of HFE SNPs and dietary intake with hemoglobin, anemia risk, and MRI-derived liver iron levels as markers of systemic iron status. We compared brain QSM for rs1799945 and rs1800562 homozygotes and rs1799945/rs1800562 compound heterozygotes relative to control genotype subjects without either HFE SNP using ANCOVA and Tukey-Kramer post-hoc testing. Significance was set at false discovery rate (FDR) <0.05.</p>
RESULTS: Intake of dietary heme iron and both HFE SNPs were associated with increased QSM and decreased T2* MRI intensities (FDR<0.05), a pattern associated with increased brain iron levels. Non-heme iron intake was associated with a slight, but statistically significant, decrease in QSM and increase in T2* intensity, which is consistent with less brain iron. Both SNPs and heme iron intake were associated with higher hemoglobin and MRI-derived liver iron levels. Adjusted mean QSM intensity was generally highest for rs1800562 homozygotes and mostly higher in rs1799945 homozygotes and rs1799945/rs1800562 compound heterozygotes compared to control genotype.</p>
CONCLUSIONS: Dietary heme iron intake and SNPs linked to hemochromatosis are associated with altered brain MRI intensities consistent with elevated brain iron.</p>
7 Authors
- Cameron J Cardona
- Riju Sigdel
- Parker R Johnson
- Yoo Kim
- McKale R Montgomery
- Sam R Emerson
- Winyoo Chowanadisai
1 Application
| Application ID | Title |
|---|---|
| 88625 | Role of micronutrient metabolism and genetics in health outcomes and biomarkers |
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