A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity - PubMed (original) (raw)
A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity
A Heinz et al. Biol Psychiatry. 2000.
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]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.
Comment in
- Cautionary note: complex (dys) function of the serotonin transporter.
Battaglia M, Ogliari A, Maffei C, Marino C, Molteni M, Nobile M. Battaglia M, et al. Biol Psychiatry. 2000 Aug 15;48(4):334-5. doi: 10.1016/s0006-3223(00)00937-9. Biol Psychiatry. 2000. PMID: 11023299 No abstract available.
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