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Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project

Lookup NU author(s): Dr Christopher Morris, Dr Reinhard Heun

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Abstract

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.


Publication metadata

Author(s): Lehmann DJ, Schuur M, Warden DR, Hammond N, Belbin O, Kolsch H, Lehmann MG, Wilcock GK, Brown K, Kehoe PG, Morris CM, Barker R, Coto E, Alvarez V, Deloukas P, Mateo I, Gwilliam R, Combarros O, Arias-Vasquez A, Aulchenko YS, Ikram MA, Breteler MM, van Duijn CM, Oulhaj A, Heun R, Cortina-Borja M, Morgan K, Robson K, Smith AD

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2012

Volume: 33

Issue: 1

Pages: 202.e1

Print publication date: 02/09/2010

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier Inc.

URL: http://dx.doi.org/10.1016/j.neurobiolaging.2010.07.018

DOI: 10.1016/j.neurobiolaging.2010.07.018


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