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

Andreas Heinz, Douglas W. Jones, Chiara Mazzanti, David Goldman, Paul Ragan, Dan Hommer, Markku Linnoila, Daniel R. Weinberger

Research output: Contribution to journalArticle

Abstract

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]β-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. Copyright (C) 2000.

Original languageEnglish (US)
Pages (from-to)643-649
Number of pages7
JournalBiological psychiatry
Volume47
Issue number7
DOIs
StatePublished - Apr 1 2000
Externally publishedYes

Keywords

  • Alcoholism
  • Gene expression
  • SLC6A4
  • SPECT
  • Serotonin transporters
  • β-CIT

ASJC Scopus subject areas

  • Biological Psychiatry

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