Alzheimer's disease: Case-control association study of polymorphisms in ACHE, CHAT, and BCHE genes in a Sardinian sample

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2007-10, Vol.144B (7), p.895-899
• Main Authors: Piccardi, Mariapaola, Congiu, Donatella, Squassina, Alessio, Manconi, Francesca, Putzu, Paolo Francesco, Mereu, Rosa Maria, Chillotti, Caterina, Del Zompo, Maria
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - genetics; Adult and adolescent clinical studies; Aged; Aged, 80 and over; Alzheimer Disease - enzymology; Alzheimer Disease - ethnology; Alzheimer Disease - genetics; Apolipoprotein E4 - genetics; Biological and medical sciences; Butyrylcholinesterase - genetics; candidate genes; Case-Control Studies; Choline O-Acetyltransferase - genetics; cholinergic system; Cholinesterase Reactivators - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Genetic Predisposition to Disease; Genetics, Population; Genotype; Humans; Italy; Male; Medical genetics; Medical sciences; Neurology; Organic mental disorders. Neuropsychology; Polymorphism, Single Nucleotide; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Sardinian ethnicity
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30548

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‐ε4 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 ε4 allele and AD (P