No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by PET.
Synapse
; 48(4): 184-8, 2003 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-12687637
ABSTRACT
The human serotonin transporter (5-HTT) gene has a polymorphism in the 5'-flanking promoter region that is called the serotonin transporter gene-linked polymorphic region (5-HTTLPR). In lymphoblast cell lines, the promoter activity of the 5-HTT gene is dependent on 5-HTTLPR allelic variants. The transcriptional activity of the l allele was more than twice as high as that of the s allele. The s allele is considered to be associated with mood disorders and anxiety-related personality traits. To evaluate the functional differences of 5-HTTLPR in the brain in vivo, we examined the allelic variations of 5-HTTLPR and measured 5-HTT binding in the living human brain using positron emission tomography (PET) with C(11)-labeled trans-1, 2, 4, 5, 6, 10-beta-hexahydro-6-[4-(methylthio) phenyl]pyrrolo[2,1-a]isoquinoline (McN5652) as a ligand. Twenty-seven healthy male subjects participated in this study. Although the human lymphoblast cells with the l/l genotype was reported to produce higher concentrations of both mRNA and protein of 5-HTT than those with the l/s or s/s genotype in a human lymphoblast in vitro study, 5-HTT binding in vivo was not significantly different among subjects with the three genotypes (l/l 0.842 +/- 0.184, l/s 0.708 +/- 0.118, s/s 0.825 +/- 0.209). In conclusion, this study does not support the assumption that the genotype-dependent differences of 5-HTTLPR directly contributes to the regulation of the 5-HTT binding site in the living human brain.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
/
Encéfalo
/
Glicoproteínas de Membrana
/
Proteínas de Transporte
/
Tomografia Computadorizada de Emissão
/
Regiões Promotoras Genéticas
/
Alelos
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Synapse
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Japão