title: Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (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 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.
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
authors.forename: Lynnette J
authors.initials: LJ
authors.lastname: Cook
authors.forename: Luk W
authors.initials: LW
authors.lastname: Ho
authors.forename: Alison E
authors.initials: AE
authors.lastname: Taylor
authors.forename: Carol
authors.initials: C
authors.lastname: Brayne
authors.forename: John Grimley
authors.initials: JG
authors.lastname: Evans
authors.forename: John
authors.initials: J
authors.lastname: Xuereb
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: Antonia
authors.initials: A
authors.lastname: Pritchard
authors.forename: Helen
authors.initials: H
authors.lastname: Lemmon
authors.forename: David
authors.initials: D
authors.lastname: Mann
authors.forename: David
authors.initials: D
authors.lastname: St Clair
authors.forename: Dragana
authors.initials: D
authors.lastname: Turic
authors.forename: Paul
authors.initials: P
authors.lastname: Hollingworth
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Moore
authors.forename: Luke
authors.initials: L
authors.lastname: Jehu
authors.forename: Nicola
authors.initials: N
authors.lastname: Archer
authors.forename: Sarah
authors.initials: S
authors.lastname: Walter
authors.forename: Catherine
authors.initials: C
authors.lastname: Foy
authors.forename: Amanda
authors.initials: A
authors.lastname: Edmondson
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Corinne
authors.initials: C
authors.lastname: Lendon
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic