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5-HT1A gene promoter polymorphism and [ 18F]MPPF binding potential in healthy subjects: a PET
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@MISC{Lothe_5-ht1agene,
author = {Amélie Lothe and Claudette Boni and Nicolas Costes and Rine Bouvard and Philip Gorwood and Franck Lavenne and Marion Alvarez},
title = {5-HT1A gene promoter polymorphism and [ 18F]MPPF binding potential in healthy subjects: a PET},
year = {}
}
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Abstract
Background: Previous Positron Emission Tomography (PET) studies of 5-HT1A receptors have shown an influence of several genetic factors, including the triallelic serotonin transporter gene-linked polymorphic region on the binding potential (BPND) of these receptors. The aim of our study was to investigate the relationship between a 5-HT1A promoter polymorphism and the binding potential of another selective 5-HT1A receptor antagonist, [ 18F]MPPF, in healthy subjects. Methods: Thirty-five volunteers, including 23 women, underwent an [ 18F]MPPF scan and were genotyped for both the C(-1019)G 5-HT1A promoter polymorphism and the triallelic serotonin transporter gene-linked polymorphic region. We used a simplified reference tissue model to generate parametric images of BPND. Whole brain Statistical Parametric Mapping and raphe nuclei region of interest analyses were performed to look for an association of [ 18F]MPPF BPND with the C(-1019)G 5-HT1A promoter polymorphism. Results: Among the 35 subjects, 5-HT1A promoter genotypes occurred with the following frequencies: three G/G, twenty-one G/C, and eleven C/C. No difference of [ 18F]MPPF BPND between groups was observed, except for two women who were homozygote carriers for the G allele and showed greater binding potential compared to other agematched women over the frontal and temporal neocortex. However, the biological relevance of this result remains uncertain due to the very small number of subjects with a G/G genotype. These findings were not modified by excluding individuals carrying the S/S genotype of the serotonin transporter gene-linked polymorphic region. Conclusions: We failed to observe an association between the C(-1019)G 5-HT1A promoter polymorphism and [ 18F]MPPF binding in healthy subjects. However our data suggest that the small number of women homozygote for the G allele might have greater [ 18F]MPPF BPND relative to other individuals. This finding should be confirmed in a larger sample.
Keyphrases
healthy subject 5-ht1a promoter polymorphism mppf bpnd 5-ht1a gene promoter polymorphism small number 5-ht1a receptor previous positron emission tomography interest analysis parametric image serotonin transporter gene-linked polymorphic region several genetic factor agematched woman thirty-five volunteer temporal neocortex homozygote carrier 5-ht1a promoter genotype whole brain statistical parametric mapping following frequency mppf scan biological relevance nucleus region selective 5-ht1a receptor antagonist simplified reference tissue model
