Candidate gene association studies of the α4 (CHRNA4) and β2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease

被引：38

作者：

Cook, LJ

Ho, LW

Taylor, AE

Brayne, C

Evans, JG

Xuereb, J

Cairns, NJ

Pritchard, A

Lemmon, H

Mann, D

Clair, DS

Turic, D

Hollingworth, P

Moore, PJ

Jehu, L

Archer, N

Walter, S

Foy, C

Edmondson, A

Powell, J

Lovestone, S

Owen, MJ

Williams, J

Lendon, C

Rubinsztein, DC

机构：

[1] Addenbrookes Hosp, Dept Med Genet, Cambridge Inst Med Res, Cambridge CB2 2XY, England

[2] Great Ormond St Hosp Sick Children, Reg Mol Genet Lab, Camelia Bot Labs, London, England

[3] Univ Forvie Site, Dept Hlth & Primary Care, Addenbrookes Hosp, Cambridge, England

[4] Radcliffe Infirm, Dept Clin Geratol, Oxford OX2 6HE, England

[5] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England

[6] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA

[7] Univ Birmingham, Sch Med, Dept Psychiat, Div Neurosci, Birmingham B15 2TT, W Midlands, England

[8] Royal Comhill Hosp, Clin Res Ctr, Aberdeen, Scotland

[9] Hope Hosp, Greater Manchester Neurosci Ctr, Manchester, Lancs, England

[10] Sch Med, Dept Mental Hlth, Aberdeen, Scotland

[11] Univ Wales Coll Cardiff, Coll Med, Dept Psychol Med, Cardiff CF1 3NS, S Glam, Wales

[12] Inst Psychiat, London, England

来源：

NEUROSCIENCE LETTERS | 2004年 / 358卷 / 02期

基金：

英国医学研究理事会;

关键词：

nicotinic acetylcholine receptor; Alzheimer's disease; polymorphism; Genetic Association; Medical Research Council Cognitive Function and Ageing Study (MRC-COGFA);

D O I：

10.1016/j.neulet.2004.01.016

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Consistent deficits in the cholinergic system are evident in Alzheimer's disease (AD) patients, including selective loss of alpha4beta2 nicotinic acetylcholine receptors in the brains of AD patients. Knockout mice for the beta2 subunit have impaired neuronal survival in ageing. Accordingly, we have analysed polymorphisms in the genes that encode the alpha4 and beta2 subunits, CHRNA4 and CHRNB2 respectively, for genetic associations with late-onset AD. A significant association for disease was observed for a non-coding polymorphism in CHRNB2 (odds ratio = 0.57, 95% confidence interval = 0.35-0.95, P = 0.024). Replication analysis was performed in two further sample sets. While these did not individually yield significant results, a significant association remained when all samples were pooled (odds ratio = 0.70, 95% confidence interval = 0.52-0.95, P = 0.019). These data suggest that this variant warrants further examination in large case-control series. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

引用

页码：142 / 146

页数：5

共 23 条

[1] THE CHOLINERGIC HYPOTHESIS OF GERIATRIC MEMORY DYSFUNCTION [J].