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PMID: 15758168 Published · ppublish English Comparative Study Journal Article

A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 25 ·No. 10 ·2005-03-09 ·Pages 2586-90

David SP, Murthy NV, Rabiner EA, Munafó MR, Johnstone EC, Jacob R, Walton RT, Grasby PM

Abstract

In humans, 5-HT1A receptors are implicated in anxiety and depressive disorders and their treatment. However, the physiological and genetic factors controlling 5-HT1A receptor expression are undetermined in health and disease. In this study, the influence of two genetic factors on 5-HT1A receptor expression in the living human brain was assessed using the 5-HT1A-selective positron emission tomography (PET) ligand [11C]WAY 100635. After the genotyping of 140 healthy volunteers to study population frequencies of known single nucleotide polymorphisms (SNPs) in the 5-HT1A receptor gene, the influence of the common SNP [(-1018) C>G] on 5-HT1A receptor expression was examined in a group of 35 healthy individuals scanned with [11C]WAY 100635. In the PET group, we also studied the influence of a common variable number tandem repeat polymorphism [short (S) and long (L) alleles] of the 5-HT transporter (5-HTT) gene on 5-HT1A receptor density. Whereas, the 5-HT1A receptor genotype did not show any significant effects on [11C]WAY 100635 binding, 5-HT1A receptor binding potential values were lower in all brain regions in subjects with 5-HTTLPR short (SS or SL) genotypes than those with long (LL) genotypes. Although the PET groups are necessarily a small sample size for a genetic association study, our results demonstrate for the first time that a functional polymorphism in the 5-HTT gene, but not the 5-HT1A receptor gene, affects 5-HT1A receptor availability in man. The results may offer a plausible physiological mechanism underlying the association between 5-HTTLPR genotype, behavioral traits, and mood states.

MeSH Terms
Adult Cohort Studies Female Gene Frequency/genetics Genetic Variation/genetics Humans Male Middle Aged Piperazines/metabolism Polymorphism, Genetic/genetics Protein Binding/genetics Pyridines/metabolism Receptor, Serotonin, 5-HT1A/genetics,metabolism Serotonin Plasma Membrane Transport Proteins/genetics,physiology
Chemicals
Piperazines Pyridines Serotonin Plasma Membrane Transport Proteins Receptor, Serotonin, 5-HT1A N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
David Sean P
Department of Clinical Pharmacology, Cancer Research United Kingdom General Practice Research Group, University of Oxford, Oxford OX2 6HE, United Kingdom.
Murthy Naga Venkatesha
Rabiner Eugenii A
Munafó Marcus R
Johnstone Elaine C
Jacob Robyn
Walton Robert T
Grasby Paul M
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.3769-04.2005
Published
2005-03-09
Pages
2586-90
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC1942077
Subset
IM
Grants
NIDA NIH HHS · K08 DA014276-01A2 · United States
NIDA NIH HHS · K08 DA014276-05 · United States
NIDA NIH HHS · K08 DA014276-03 · United States
NIDA NIH HHS · K08 DA014276 · United States
NIDA NIH HHS · K08 DA014276-02 · United States
NIDA NIH HHS · K08 DA014276-04 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.3769-04.2005 PMC Full Text View journal details
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