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Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease

Cook, Lynnette J., Ho, Luk W., Taylor, Alison E., 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 John, Williams, Julie, Lendon, Corinne and Rubinsztein, David C. 2004. Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease. Neuroscience Letters 358 (2) , pp. 142-146. 10.1016/j.neulet.2004.01.016

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
ISSN: 0304-3940
Last Modified: 04 Jun 2017 08:38
URI: http://orca.cf.ac.uk/id/eprint/81715

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