Author: Heinz, A.; Jones, D.W.; Mazzanti, C.; Goldman, D.; Ragan, P.; Hommer, D.; Linnoila, M.; Weinberger, D.R.
Description: 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.
Subject Headings: Adult; Alcohol-Induced Disorders, Nervous System/genetics/metabolism; Alcoholism/diagnostic imaging/genetics/metabolism; Alleles; Carrier Proteins/genetics/metabolism; Case-Control Studies; Cocaine/analogs & derivatives; Ethanol/toxicity; Gene Expression; Genotype; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins/genetics/metabolism; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins/genetics/metabolism; Polymerase Chain Reaction; Serotonin/genetics/metabolism; Serotonin Plasma Membrane Transport Proteins; Temperance; Tomography, Emission-Computed, Single-Photon
Keywords: A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity
Publication year: 2000
Journal or book title: Biological Psychiatry
Volume: 47
Issue: 7
Pages: 643-649
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Type: Journal Article
Serial number: 2613