Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Oct;43(10):e52.
doi: 10.1136/jmg.2006.040519.

Iron genes, iron load and risk of Alzheimer's disease

D J Lehmann, M Worwood, R Ellis, V L J Wimhurst, A T Merryweather-Clarke, D R Warden, A D Smith, K J H Robson

Iron genes, iron load and risk of Alzheimer's disease

D J Lehmann et al. J Med Genet. 2006 Oct.

Abstract

Background: Compound heterozygotes of the haemochromatosis gene (HFE) variants, H63D and C282Y, have raised transferrin saturation compared with that in the wild type. In the cohort of the Oxford Project To Investigate Memory and Ageing (OPTIMA), bicarriers of the HFE C282Y and the transferrin C2 gene variants are at five times greater risk of developing Alzheimer's disease; the addition of HFE H63D may raise the risk still further.

Objective: To investigate transferrin saturation by HFE and transferrin genotype among people without dementia-that is, controls and those with mild cognitive impairment (MCI)-and also among those with Alzheimer's disease.

Methods: Serum iron status and genotype were examined of 177 patients with Alzheimer's disease, 69 patients with MCI and 197 controls from the OPTIMA cohort.

Results: Although each of these variants alone had relatively little effect on iron status, the combination of either HFE C282Y and HFE H63D or of HFE C282Y and transferrin C2 markedly raised transferrin saturation in those without dementia, but had little effect in those with mature Alzheimer's disease.

Conclusions: These combinations may raise the risk for Alzheimer's disease, owing to higher iron loads and therefore oxidative stress in the preclinical phase. If replicated, these findings will have implications for the prevention of Alzheimer's disease.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Merryweather‐Clarke A T, Worwood M, Parkinson L, Mattock C, Pointon J J, Shearman J D, Robson K J. The effect of HFE mutations on serum ferritin and transferrin saturation in the Jersey population. Br J Haematol 1998101369–373. - PubMed
    1. Beutler E, Felitti V, Gelbert T, Ho N. The effect of HFE genotypes on measurements of iron overload in patients attending a health appraisal clinic. Ann Intern Med 2000133329–337. - PubMed
    1. Jackson H A, Carter K, Darke C, Guttridge M G, Ravine D, Hutton R D, Napier J A, Worwood M. HFE mutations, iron deficiency and overload in 10,500 blood donors. Br J Haematol 2001114474–484. - PubMed
    1. Rossi E, Bulsara M K, Olynyk J K, Cullen D J, Summerville L, Powell L W. Effect of hemochromatosis genotype and lifestyle factors on iron and red cell indices in a community population. Clin Chem 200147202–208. - PubMed
    1. Beutler E, Felitti V, Gelbart T, Waalen J. Haematological effects of the C282Y HFE mutation in homozygous and heterozygous states among subjects of northern and southern European ancestry. Br J Haematol 2003120887–893. - PubMed

Publication types

MeSH terms