5-HT(1A )gene promoter polymorphism and [(18)F]MPPF binding potential in healthy subjects: a PET study

BACKGROUND: Previous Positron Emission Tomography (PET) studies of 5-HT(1A )receptors have shown an influence of several genetic factors, including the triallelic serotonin transporter gene-linked polymorphic region on the binding potential (BP(ND)) of these receptors. The aim of our study was to investigate the relationship between a 5-HT(1A )promoter polymorphism and the binding potential of another selective 5-HT(1A )receptor antagonist, [(18)F]MPPF, in healthy subjects. METHODS: Thirty-five volunteers, including 23 women, underwent an [(18)F]MPPF scan and were genotyped for both the C(-1019)G 5-HT(1A )promoter polymorphism and the triallelic serotonin transporter gene-linked polymorphic region. We used a simplified reference tissue model to generate parametric images of BP(ND). Whole brain Statistical Parametric Mapping and raphe nuclei region of interest analyses were performed to look for an association of [(18)F]MPPF BP(ND )with the C(-1019)G 5-HT(1A )promoter polymorphism. RESULTS: Among the 35 subjects, 5-HT(1A )promoter genotypes occurred with the following frequencies: three G/G, twenty-one G/C, and eleven C/C. No difference of [(18)F]MPPF BP(ND )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-HT(1A )promoter polymorphism and [(18)F]MPPF binding in healthy subjects. However our data suggest that the small number of women homozygote for the G allele might have greater [(18)F]MPPF BP(ND )relative to other individuals. This finding should be confirmed in a larger sample.