No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by pet

Kunihiko Shioe, Tetsuya Ichimiya, Tetsuya Suhara, Akihiro Takano, Yasuhiko Sudo, Fumihiko Yasuno, Masami Hirano, Manabu Shinohara, Masato Kagami, Yoshiro Okubo, Masahiro Nankai, Shigenobu Kanba

Research output: Contribution to journalArticle

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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 C11-labeled trans-1, 2, 4, 5, 6, 10-β-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.

Original languageEnglish
Pages (from-to)184-188
Number of pages5
JournalSynapse
Volume48
Issue number4
DOIs
Publication statusPublished - Jun 15 2003
Externally publishedYes

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Pets
Genetic Promoter Regions
Genotype
Brain
Genes
Alleles
5' Flanking Region
Mood Disorders
Positron-Emission Tomography
Personality
Healthy Volunteers
Anxiety
Binding Sites
Ligands
Cell Line
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by pet. / Shioe, Kunihiko; Ichimiya, Tetsuya; Suhara, Tetsuya; Takano, Akihiro; Sudo, Yasuhiko; Yasuno, Fumihiko; Hirano, Masami; Shinohara, Manabu; Kagami, Masato; Okubo, Yoshiro; Nankai, Masahiro; Kanba, Shigenobu.

In: Synapse, Vol. 48, No. 4, 15.06.2003, p. 184-188.

Research output: Contribution to journalArticle

Shioe, K, Ichimiya, T, Suhara, T, Takano, A, Sudo, Y, Yasuno, F, Hirano, M, Shinohara, M, Kagami, M, Okubo, Y, Nankai, M & Kanba, S 2003, 'No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by pet', Synapse, vol. 48, no. 4, pp. 184-188. https://doi.org/10.1002/syn.10204
Shioe, Kunihiko ; Ichimiya, Tetsuya ; Suhara, Tetsuya ; Takano, Akihiro ; Sudo, Yasuhiko ; Yasuno, Fumihiko ; Hirano, Masami ; Shinohara, Manabu ; Kagami, Masato ; Okubo, Yoshiro ; Nankai, Masahiro ; Kanba, Shigenobu. / No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by pet. In: Synapse. 2003 ; Vol. 48, No. 4. pp. 184-188.
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