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

Lynnette J. Cook, Luk W. Ho, Carol Brayne, John Grimley Evans, John Xuereb, Nigel J. Cairns, Antonia Pritchard, Helen Lemmon, David Mann, David St Clair, Dragana Turic, Paul Hollingworth, Pamela J. Moore, Luke Jehu, Nicola Archer, Sarah Walter, Catherine Foy, Amanda Edmondson, John Powell, Simon Lovestone & 5 others Michael J. Owen, Julie Williams, Corinne Lendon, David C. Rubinsztein, Alison Taylor

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Consistent deficits in the cholinergic system are evident in Alzheimer's disease (AD) patients, including selective loss of α4β2 nicotinic acetylcholine receptors in the brains of AD patients. Knockout mice for the β2 subunit have impaired neuronal survival in ageing. Accordingly, we have analysed polymorphisms in the genes that encode the α4 and β2 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.

Original languageEnglish
Pages (from-to)142-146
Number of pages5
JournalNeuroscience Letters
Volume358
Issue number2
DOIs
Publication statusPublished - 25 Mar 2004
Externally publishedYes

Fingerprint

Nicotinic Receptors
Genetic Association Studies
Alzheimer Disease
Odds Ratio
Confidence Intervals
Genes
Brain Diseases
Knockout Mice
Cholinergic Agents

Cite this

Cook, Lynnette J. ; Ho, Luk W. ; Brayne, Carol ; Evans, John Grimley ; Xuereb, John ; Cairns, Nigel J. ; Pritchard, Antonia ; Lemmon, Helen ; Mann, David ; St Clair, David ; Turic, Dragana ; Hollingworth, Paul ; Moore, Pamela J. ; Jehu, Luke ; Archer, Nicola ; Walter, Sarah ; Foy, Catherine ; Edmondson, Amanda ; Powell, John ; Lovestone, Simon ; Owen, Michael J. ; Williams, Julie ; Lendon, Corinne ; Rubinsztein, David C. ; Taylor, Alison. / Candidate gene association studies of the α4 (CHRNA4) and β2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease. In: Neuroscience Letters. 2004 ; Vol. 358, No. 2. pp. 142-146.
@article{da596ae9cb454eba9db77c2d090f141c,
title = "Candidate gene association studies of the α4 (CHRNA4) and β2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease",
abstract = "Consistent deficits in the cholinergic system are evident in Alzheimer's disease (AD) patients, including selective loss of α4β2 nicotinic acetylcholine receptors in the brains of AD patients. Knockout mice for the β2 subunit have impaired neuronal survival in ageing. Accordingly, we have analysed polymorphisms in the genes that encode the α4 and β2 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.",
keywords = "Alzheimer's disease, Genetic Association, Medical Research Council Cognitive Function and Ageing Study (MRC-COGFA), Nicotinic acetylcholine receptor, Polymorphism",
author = "Cook, {Lynnette J.} and Ho, {Luk W.} and Carol Brayne and Evans, {John Grimley} and John Xuereb and Cairns, {Nigel J.} and Antonia Pritchard and Helen Lemmon and David Mann and {St Clair}, David and Dragana Turic and Paul Hollingworth and Moore, {Pamela J.} and Luke Jehu and Nicola Archer and Sarah Walter and Catherine Foy and Amanda Edmondson and John Powell and Simon Lovestone and Owen, {Michael J.} and Julie Williams and Corinne Lendon and Rubinsztein, {David C.} and Alison Taylor",
year = "2004",
month = "3",
day = "25",
doi = "10.1016/j.neulet.2004.01.016",
language = "English",
volume = "358",
pages = "142--146",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier",
number = "2",

}

Cook, LJ, Ho, LW, Brayne, C, Evans, JG, Xuereb, J, Cairns, NJ, Pritchard, A, Lemmon, H, Mann, D, St Clair, D, 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 & Taylor, A 2004, 'Candidate gene association studies of the α4 (CHRNA4) and β2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease', Neuroscience Letters, vol. 358, no. 2, pp. 142-146. https://doi.org/10.1016/j.neulet.2004.01.016

Candidate gene association studies of the α4 (CHRNA4) and β2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease. / Cook, Lynnette J.; Ho, Luk W.; Brayne, Carol; Evans, John Grimley; Xuereb, John; Cairns, Nigel J.; Pritchard, Antonia; Lemmon, Helen; Mann, David; St Clair, David; Turic, Dragana; Hollingworth, Paul; Moore, Pamela J.; Jehu, Luke; Archer, Nicola; Walter, Sarah; Foy, Catherine; Edmondson, Amanda; Powell, John; Lovestone, Simon; Owen, Michael J.; Williams, Julie; Lendon, Corinne; Rubinsztein, David C.; Taylor, Alison.

In: Neuroscience Letters, Vol. 358, No. 2, 25.03.2004, p. 142-146.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Candidate gene association studies of the α4 (CHRNA4) and β2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease

AU - Cook, Lynnette J.

AU - Ho, Luk W.

AU - Brayne, Carol

AU - Evans, John Grimley

AU - Xuereb, John

AU - Cairns, Nigel J.

AU - Pritchard, Antonia

AU - Lemmon, Helen

AU - Mann, David

AU - St Clair, David

AU - Turic, Dragana

AU - Hollingworth, Paul

AU - Moore, Pamela J.

AU - Jehu, Luke

AU - Archer, Nicola

AU - Walter, Sarah

AU - Foy, Catherine

AU - Edmondson, Amanda

AU - Powell, John

AU - Lovestone, Simon

AU - Owen, Michael J.

AU - Williams, Julie

AU - Lendon, Corinne

AU - Rubinsztein, David C.

AU - Taylor, Alison

PY - 2004/3/25

Y1 - 2004/3/25

N2 - Consistent deficits in the cholinergic system are evident in Alzheimer's disease (AD) patients, including selective loss of α4β2 nicotinic acetylcholine receptors in the brains of AD patients. Knockout mice for the β2 subunit have impaired neuronal survival in ageing. Accordingly, we have analysed polymorphisms in the genes that encode the α4 and β2 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.

AB - Consistent deficits in the cholinergic system are evident in Alzheimer's disease (AD) patients, including selective loss of α4β2 nicotinic acetylcholine receptors in the brains of AD patients. Knockout mice for the β2 subunit have impaired neuronal survival in ageing. Accordingly, we have analysed polymorphisms in the genes that encode the α4 and β2 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.

KW - Alzheimer's disease

KW - Genetic Association

KW - Medical Research Council Cognitive Function and Ageing Study (MRC-COGFA)

KW - Nicotinic acetylcholine receptor

KW - Polymorphism

UR - http://www.scopus.com/inward/record.url?scp=12144291280&partnerID=8YFLogxK

UR - https://www.journals.elsevier.com/neuroscience-letters

U2 - 10.1016/j.neulet.2004.01.016

DO - 10.1016/j.neulet.2004.01.016

M3 - Article

VL - 358

SP - 142

EP - 146

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 2

ER -