Affiliations: Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
Correspondence:
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Address for correspondence: Akinori Ueki, MD, PhD, Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. Tel.: +81 798 45 6051; Fax: +81 798 45 6053; E-mail: [email protected].
Abstract: The purpose of the present study was to confirm an association of functional polymorphism within the serotonin transporter (5-HTT) gene with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) in mild AD. Apolipoprotein E (ApoE) gene polymorphism and 2 types of functional polymorphism in the 5-HTT gene, 5-HTT-linked polymorphic region (5-HTTLPR) and a 5-HTT variable number of tandem repeats sequence (5-HTTVNTR) were analyzed longitudinally in outpatients with mild AD to find out whether there was a relation between any such polymorphisms and the occurrence of BPSD. No significant differences in genotype distribution or allele frequencies were identified for 5-HTTLPR or 5-HTTVNTR between AD patients and age- and sex-matched non-demented controls regardless of ApoE ε4 allele. No significant differences were noted in 5-HTTLPR genotype or allele distributions between AD patients with or without BPSD. However, significant associations were observed between presence of 5-HTTVNTR allele 10 and BPSD or aggressiveness. This difference was independent of the presence of the ApoE ε4 allele. As a result, 5-HTT polymorphisms are unlikely to play any substantial role in susceptibility to AD. Conversely, 5-HTTVNTR influences the risk of developing BPSD or aggressiveness and genetic variations in the 5-HTT gene may be involved in the development of symptomatology for mild AD.
Keywords: Serotonin transporter, genetic, polymorphism, Alzheimer's disease, behavioral and psychological symptoms of dementia, aggressiveness
