5-HT1A gene promoter polymorphism and [18F]MPPF binding potential in healthy subjects: a PET study.
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 age-matched 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.
Lothe
Amélie
A
CTRS-IDEE, Lyon, France. amelie.lothe@cermep.fr
Boni
Claudette
C
Costes
Nicolas
N
Bouvard
Sandrine
S
Gorwood
Philip
P
Lavenne
Franck
F
Alvarez
Marion
M
Ryvlin
Philippe
P
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006304:Health Status; D006720:Homozygote; D006801:Humans; D008297:Male; D010879:Piperazines / Q000378:metabolism / Q000493:pharmacokinetics*; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011725:Pyridines / Q000378:metabolism / Q000493:pharmacokinetics*; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000378:metabolism / Q000493:pharmacokinetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012727:Sex Characteristics
D010879:Piperazines; D011725:Pyridines; C493230:SLC6A4 protein, human; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; C416325:4-(2'-methoxyphenyl)-1-(2'-(N-2'-pyridinyl)-p-(18F)fluorobenzamido )ethylpiperazine