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

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 APOEε4 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.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Lehmann DJ,Schuur M,Warden DR,Hammond N,Belbin O,Kölsch 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-Vásquez A,Aulchenko YS,Ikram MA

doi

10.1016/j.neurobiolaging.2010.07.018

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

202.e1-13

issue

1

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(10)00326-X

journal_volume

33

pub_type

杂志文章

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