A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity

Biol Psychiatry. 2000 Apr 1;47(7):643-9. doi: 10.1016/s0006-3223(99)00171-7.


Background: Genetic variation of the promoter for the serotonin transporter (5-HTT) gene has been associated with its functional capacity. In vitro, carriers of a short allele (s-carriers) of the 5-HTT promoter display significant reduction in 5-HTT capacity. Dysfunction of 5-HTT has been observed in alcoholic individuals. We assessed whether the allelic constitution of the 5-HTT gene is associated with reduced serotonin transporter availability among alcoholic individuals.

Methods: We genotyped the 5-HTT promoter region and measured the availability of serotonin transporter protein with [I-123]beta-CIT SPECT in the raphe area in 14 abstinent male alcoholic subjects and 8 age-matched control subjects of European American descent.

Results: Among control subjects, the ratio of in vivo 5-HTT availability for ll-homozygous individuals relative to s-carriers was comparable to serotonin uptake ratios measured in vitro. There was a significant interaction of diagnosis and 5-HTT promoter genotype on 5-HTT availability (p <.01). Among controls, ll-homozygous individuals displayed a significant increase as compared with s-carriers. The availability of raphe 5-HTT was significantly reduced in ll-homozygous alcoholic individuals and was negatively correlated with their amount of alcohol consumption. Among s-carriers, 5-HTT availability did not differ significantly between control and alcoholic subjects.

Conclusions: Our preliminary findings suggest an association between 5-HTT allelic constitution and in vivo measurements of human serotonin transporter availability, and a potentially selective susceptibility of ll-homozygous individuals to the neurotoxic effects of chronic excessive alcohol consumption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcohol-Induced Disorders, Nervous System / genetics
  • Alcohol-Induced Disorders, Nervous System / metabolism*
  • Alcoholism / diagnostic imaging
  • Alcoholism / genetics*
  • Alcoholism / metabolism*
  • Alleles
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Case-Control Studies
  • Cocaine / analogs & derivatives
  • Ethanol / toxicity*
  • Gene Expression
  • Genotype
  • Humans
  • Iodine Radioisotopes
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Polymerase Chain Reaction
  • Serotonin / genetics
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins
  • Temperance
  • Tomography, Emission-Computed, Single-Photon


  • Carrier Proteins
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Ethanol
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Cocaine