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

Diego Albani, Letizia Polito, Francesca Prato, Serena Rodilossi, Eleonora Ateri, Daniela Galimberti, Elio Scarpini, Francesca Clerici, Claudio Mariani, Gianluigi Forloni

Research output: Contribution to journalArticle

Abstract

Alzheimers 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 (A→G). 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.

Original languageEnglish
Article number312341
JournalInternational Journal of Alzheimer's Disease
DOIs
Publication statusPublished - 2011

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Serotonin Plasma Membrane Transport Proteins
Meta-Analysis
Alzheimer Disease
Alleles
Population
Serotonin
Odds Ratio
Behavioral Symptoms
Memory Disorders
Genetic Promoter Regions
Neurodegenerative Diseases
Italy
Dementia
Disease Progression
Psychology
Genes

ASJC Scopus subject areas

  • Clinical Neurology
  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Ageing
  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

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title = "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",
abstract = "Alzheimers 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 (A→G). 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.",
author = "Diego Albani and Letizia Polito and Francesca Prato and Serena Rodilossi and Eleonora Ateri and Daniela Galimberti and Elio Scarpini and Francesca Clerici and Claudio Mariani and Gianluigi Forloni",
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T1 - 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

AU - Albani, Diego

AU - Polito, Letizia

AU - Prato, Francesca

AU - Rodilossi, Serena

AU - Ateri, Eleonora

AU - Galimberti, Daniela

AU - Scarpini, Elio

AU - Clerici, Francesca

AU - Mariani, Claudio

AU - Forloni, Gianluigi

PY - 2011

Y1 - 2011

N2 - Alzheimers 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 (A→G). 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.

AB - Alzheimers 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 (A→G). 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.

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