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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 312341, 7 pages
Research Article

A Novel Study and Meta-Analysis of the Genetic Variation of the Serotonin Transporter Promoter in the Italian Population Do Not Support a Large Effect on Alzheimer's Disease Risk

1Department of Neuroscience, Mario Negri Institute for Pharmacological Research, 20156 Milan, Italy
2Golgi Cenci Research Center, Abbiategrasso, 20081 Milan, Italy
3Department of Neurological Sciences, University of Milan, IRCCS Fondazione Cà Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy
4Neurology Unit, Luigi Sacco Hospital, University of Milan, 20157 Milan, Italy

Received 23 November 2010; Revised 31 January 2011; Accepted 27 March 2011

Academic Editor: Lars Bertram

Copyright © 2011 Letizia Polito et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Alzheimer’s disease (AD) is a neurodegenerative disorder whose clinical onset is mainly characterized by memory loss. During AD progression, behavioral and psychological symptoms of dementia (BPSD) frequently occur. In this paper we evaluated the association between AD and the short/long (S/L) functional polymorphism of the promoter region of the 5-hydroxytryptamine (5-HT) transporter gene (SLC6A4). The S-allele shows a 2-fold reduced transcriptional rate, causing an imbalance in 5-HT intracellular availability that might in turn trigger behavioral and cognitive alterations. We also genotyped the SLC6A4 promoter functional variant rs25531 ( ). By comparing the genotypic and allelic frequencies in an Italian population of 235 AD and 207 controls, we found an association between 5-HTTLPR and AD (odds ratio for the L-allele versus the S-allele: 0.74, associated P value = .03), while no difference was found for the rs25531. A meta-analysis of studies in Italy assessing 5-HTTLPR and AD risk gave an estimation of odds ratio for the L-allele versus the S-allele of 0.85 (associated P value = .08). Overall, our findings are not supportive of a large genetic effect of the explored polymorphisms on AD risk.