Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region

Science. 1996 Nov 29;274(5292):1527-31. doi: 10.1126/science.274.5292.1527.

Abstract

Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Anxiety Disorders / genetics*
  • Carrier Proteins / genetics*
  • Cell Line
  • Female
  • Genetic Markers
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins*
  • Neurotic Disorders / genetics*
  • Nuclear Family
  • Personality Tests
  • Phenotype
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins
  • Transfection

Substances

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