Candidate gene association studies of the alpha4 (CHRNA4) and beta2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease

L. J. Cook, L. W. Horrobin, A. E. Taylor, C. Brayne, J. G. Evans, J. Xuereb, N. J. Cairns, A. Pritchard, H.a. Lemmon, D. Mann, David Malcolm St Clair, D. Turic, P. Hollingworth, P. J. Moore, L. Jehu, N. Archer, S. Walter, C. Foy, A. Edmondson, J. Powell

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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. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)142-146
Number of pages4
JournalNeuroscience Letters
Volume358
DOIs
Publication statusPublished - 2004

Keywords

  • nicotinic acetylcholine receptor
  • Alzheimer's disease
  • polymorphism
  • Genetic Association
  • Medical Research Council Cognitive Function and Ageing Study (MRC-COGFA)
  • CHOLINERGIC HYPOTHESIS
  • AMYLOID TOXICITY
  • TEMPORAL CORTEX
  • POLYMORPHISMS
  • STIMULATION
  • HIPPOCAMPUS
  • EXPRESSION
  • PROTEIN
  • RISK

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