期刊
NEUROBIOLOGY OF AGING
卷 33, 期 1, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2010.07.018
关键词
Apolipoprotein E epsilon 4; Glycosylation; Iron chelation; Microglia; Mild cognitive impairment; Neurodegeneration; Onset age; Transferrin saturation
资金
- Moulton Charitable Foundation
- NIHR Biomedical Research Centre, Oxford
- Department of Health's NIHR Biomedical Research Centres
- Medical Research Council in its capacity as the MRC Centre of Epidemiology for Child Health [G0400546]
- Erasmus Medical Center and Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly [RIDE1, RIDE2]
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- Netherlands Organisation of Scientific Research NWO [175.010.2005.011, 911-03-012]
- MRC [G0400074, G0400546, G0502157, G0900652] Funding Source: UKRI
- Alzheimers Research UK [ART-PPG2008A-3, ART-BIG2009-1] Funding Source: researchfish
- Medical Research Council [G0400546, G0900652, G0400546B, G0502157, G0400074] Funding Source: researchfish
Iron overload may contribute to the risk of Alzheimer's disease (AD). In the Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE 282Y and TF C2 in the risk of AD: synergy factor, 1.75 (95% confidence interval, 1.1-2.8, p = 0.02) in Northern Europeans. The synergy factor was 3.1 (1.4-6.9; 0.007) in subjects with the APOE epsilon 4 allele. We found another interaction, between HFE 63HH and TF -2AA, markedly modified by age. Both interactions were found mainly or only in Northern Europeans. The interaction between HFE 282Y and TF C2 has now been replicated twice, in altogether 2313 cases of AD and 7065 controls, and has also been associated with increased iron load. We therefore suggest that iron overload may be a causative factor in the development of AD. Treatment for iron overload might thus be protective in some cases. (C) 2012 Elsevier Inc. All rights reserved.
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