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
C2 - 15026168
AN - SCOPUS:12144291280
VL - 358
SP - 142
EP - 146
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 2
ER -