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

被引：46

作者：

Lehmann, Donald J. ^{[1
]}

Schuur, Maaike ^{[2
,3
]}

Warden, Donald R. ^{[1
]}

Hammond, Naomi ^{[4
]}

Belbin, Olivia ^{[5
]}

Koelsch, Heike ^{[6
]}

Lehmann, Michael G. ^{[1
]}

Wilcock, Gordon K. ^{[7
]}

Brown, Kristelle ^{[5
]}

Kehoe, Patrick G. ^{[7
]}

Morris, Chris M. ^{[8
,9
]}

Barker, Rachel ^{[7
]}

Coto, Eliecer ^{[10
]}

Alvarez, Victoria ^{[10
]}

Deloukas, Panos ^{[4
]}

Mateo, Ignacio ^{[11
,12
]}

Gwilliam, Rhian ^{[4
]}

Combarros, Onofre ^{[11
,12
]}

Arias-Vasquez, Alejandro ^{[2
,13
,14
]}

Aulchenko, Yurii S. ^{[2
]}

Ikram, M. Arfan ^{[2
]}

Breteler, Monique M. ^{[2
]}

van Duijn, Cornelia M. ^{[2
]}

Oulhaj, Abderrahim ^{[15
]}

Heun, Reinhard ^{[6
,16
]}

Cortina-Borja, Mario ^{[17
]}

Morgan, Kevin ^{[5
]}

Robson, Kathryn ^{[18
]}

Smith, A. David ^{[1
]}

机构：

[1] Univ Dept Physiol Anat & Genet, Oxford Project Investigate Memory & Ageing OPTIMA, Oxford, England

[2] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[3] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands

[4] Wellcome Trust Sanger Inst, Cambridge, England

[5] Univ Nottingham, Queens Med Ctr, Inst Genet, Sch Mol Med Sci, Nottingham NG7 2RD, England

[6] Univ Bonn, Dept Psychiat, Bonn, Germany

[7] Univ Bristol, Frenchay Hosp, Dementia Res Grp, Inst Clin Neurosci, Frenchay Bristol, England

[8] Newcastle Univ, Wolfson Unit Clin Pharmacol, Med Toxicol Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[9] Newcastle Univ, Wolfson Unit Clin Pharmacol, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[10] Univ Oviedo, Hosp Cent Asturias, E-33080 Oviedo, Spain

[11] Univ Cantabria, Neurol Serv, Marques de Valdecilla Univ Hosp, E-39005 Santander, Spain

[12] Univ Cantabria, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Marques de Valdecilla Univ Hosp, E-39005 Santander, Spain

[13] Radboud Univ Nijmegen, Dept Psychiat, Donders Inst Brain Cognit & Behav, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[14] Radboud Univ Nijmegen, Dept Psychiat, Dept Human Genet, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[15] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, OPTIMA, Oxford OX3 9DU, England

[16] Royal Derby Hosp, Derby, England

[17] UCL, Ctr Paediat Epidemiol & Biostat, Inst Child Hlth, London, England

[18] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England

来源：

NEUROBIOLOGY OF AGING | 2012年 / 33卷 / 01期

基金：

英国医学研究理事会;

关键词：

Apolipoprotein E epsilon 4; Glycosylation; Iron chelation; Microglia; Mild cognitive impairment; Neurodegeneration; Onset age; Transferrin saturation; MILD COGNITIVE IMPAIRMENT; REDOX-ACTIVE IRON; INCREASED OXIDATIVE DAMAGE; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E GENOTYPE; BRAIN FERRITIN IRON; IN-VIVO EVALUATION; HEMOCHROMATOSIS GENE; LIPID-PEROXIDATION; NEUROFIBRILLARY TANGLES;

D O I：

10.1016/j.neurobiolaging.2010.07.018

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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.

引用

页码：202.e1 / 202.e13

页数：13

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