title: Allelic variation of human serotonin transporter gene expression.
abstract: Mood, emotion, cognition, and motor functions as well as circadian and neuroendocrine rhythms, including food intake, sleep, and reproductive activity, are modulated by the midbrain raphe serotonin (5-HT) system. By directing the magnitude and duration of postsynaptic responses, carrier-facilitated 5-HT transport into and release from the presynaptic neuron are essential for the fine tuning of serotonergic neurotransmission. Interest in the mechanism of environmental factor-, disease-, and therapy-induced modification of 5-HT transporter (5-HTT) function and its impact on early brain development, event-related synaptic plasticity, and neurodegeneration is widespread and intensifying. We have recently characterized the human and murine 5-HTT genes and performed functional analyses of their 5'-flanking regulatory regions. A tandemly repeated sequence associated with the transcriptional apparatus of the human 5-HTT gene displays a complex secondary structure, represses promoter activity in nonserotonergic neuronal cells, and contains positive regulatory components. We now report a novel polymorphism of this repetitive element and provide evidence for allele-dependent differential 5-HTT promoter activity. Allelic variation in 5-HTT-related functions may play a role in the expression and modulation of complex traits and behavior.
authors.affiliation: Department of Psychiatry, University of Würzburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Heils
authors.forename: A
authors.initials: A
authors.lastname: Teufel
authors.forename: S
authors.initials: S
authors.lastname: Petri
authors.forename: G
authors.initials: G
authors.lastname: Stöber
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.forename: D
authors.initials: D
authors.lastname: Bengel
authors.forename: K P
authors.initials: KP
authors.lastname: Lesch
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012701:Serotonin / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin