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

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. Synapse 48:184–188, 2003. © 2003 Wiley‐Liss, Inc.