Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease |
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| Authors: | 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 J Williams Julie Lendon Corinne Rubinsztein David C |
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| Affiliation: | Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK. |
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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. |
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