title: Butyrylcholinesterase K variant is genetically associated with late onset Alzheimer's disease in Northern Ireland.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has been associated, sometimes controversially, with polymorphisms in a number of genes. Recently the butyrylcholinesterase K variant (BCHE K) allele has been shown to act in synergy with the apolipoprotein E epsilon4 (APOE epsilon4) allele to promote risk for AD. Most subsequent replicative studies have been unable to confirm these findings. We have conducted a case-control association study using a clinically well defined group of late onset AD patients (n=175) and age and sex matched control subjects (n=187) from the relatively genetically homogeneous Northern Ireland population to test this association. The BCHE genotypes of patients were found to be significantly different from controls (chi(2)=23.68, df=2, p<<0.001). The frequency of the K variant allele was also found to differ significantly in cases compared to controls (chi(2)=16.39, df=1, p<<0.001) leading to an increased risk of AD in subjects with this allele (OR=3.50, 95% CI 2. 20-6.07). This risk increased in subjects 75 years and older (OR=5. 50, 95% CI 2.56-11.87). At the same time the APOE epsilon4 associated risk was found to decrease from 6.70 (95% CI 2.40-19.04) in 65-74 year olds to 3.05 (95% CI 1.34-6.95) in those subjects 75 years and older. However, we detected no evidence of synergy between BCHE K and APOE epsilon4. The results from this study suggest that possession of the BCHE K allele constitutes a significant risk for AD in the Northern Ireland population and, furthermore, this risk increases with increasing age.
authors.affiliation: Department of Geriatric Medicine, The Queen's University of Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland.
authors.forename: S P
authors.initials: SP
authors.lastname: McIlroy
authors.forename: V L
authors.initials: VL
authors.lastname: Crawford
authors.forename: K B
authors.initials: KB
authors.lastname: Dynan
authors.forename: B M
authors.initials: BM
authors.lastname: McGleenon
authors.forename: M D
authors.initials: MD
authors.lastname: Vahidassr
authors.forename: J T
authors.initials: JT
authors.lastname: Lawson
authors.forename: A P
authors.initials: AP
authors.lastname: Passmore
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D002091:Butyrylcholinesterase / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D002091:Butyrylcholinesterase