Allelic variation of human serotonin transporter gene expression

J Neurochem. 1996 Jun;66(6):2621-4. doi: 10.1046/j.1471-4159.1996.66062621.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Carrier Proteins / genetics*
  • Gene Expression Regulation / genetics
  • Humans
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Molecular Sequence Data
  • Nerve Tissue Proteins*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Serotonin / genetics
  • Serotonin Plasma Membrane Transport Proteins
  • Transcription, Genetic / genetics


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin

Associated data

  • GENBANK/X76753