title: Alzheimer's disease: case-control association study of polymorphisms in ACHE, CHAT, and BCHE genes in a Sardinian sample.
abstract: Alzheimer's disease (AD) is characterized by an extensive loss of cholinergic neurons, and their cortical projections, from the basal forebrain area. The resulting reduction in cholinergic activity is associated with decreased levels of the neurotransmitter acetylcholine (ACh), decreased activity of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and increased butyrylcholinesterase (BChE) activity. In the present study, we investigated whether the BCHE, ACHE, and CHAT genes were associated with AD and the possibility of a synergistic effect with APOE-epsilon4 in a Sardinian sample. AD patients (n = 158), exclusively of Sardinian ancestry, were recruited from the Division of Geriatrics Local Health Agency 8 and Unit of Clinical Pharmacology, Department of Neurosciences, University of Cagliari. Patients were diagnosed according to DSM-IV, and National Institute of Neurologic and Communicative Disorders and Stroke-AD and Related Disorders Association (NINCDS-ADRDA) criteria for possible or probable AD. Cognitive screening was performed by means of Mini-Mental State Examination (MMSE). Healthy controls (n = 118) of Sardinian ancestry were recruited from religious and sport associations. All patients and control subjects gave informed consent for participation in the study. Single nucleotide polymorphism (SNP) analysis was performed by PCR/RFLP or the TaqMan 5' exonuclease method. Our study confirms the association between APOE epsilon4 allele and AD (P < 0.000). No significant differences were observed in allele and genotype frequencies of BCHE, ACHE, and CHAT between AD and controls. Haplotype analysis of ACHE SNPs did not reveal a significant association between ACHE and AD. Our results suggest that the AChE, ChAT, and BChE polymorphisms do not constitute a major genetic risk factor for susceptibility to AD in a Sardinian population.
authors.affiliation: Section of Clinical Pharmacology, Department of Neurosciences B.B. Brodie, University of Cagliari, 09042 Monserrato, Cagliari, Italy. piccardi@unica.it
authors.forename: Mariapaola
authors.initials: M
authors.lastname: Piccardi
authors.forename: Donatella
authors.initials: D
authors.lastname: Congiu
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
authors.forename: Francesca
authors.initials: F
authors.lastname: Manconi
authors.forename: Paolo Francesco
authors.initials: PF
authors.lastname: Putzu
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Mereu
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000208:ethnology* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D002091:Butyrylcholinesterase / Q000235:genetics*; D016022:Case-Control Studies; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D002801:Cholinesterase Reactivators / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D053327:Apolipoprotein E4; D002801:Cholinesterase Reactivators; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase