High ethanol tolerance in young adults is associated with the low-activity variant of the promoter of the human serotonin transporter gene.
Central serotonergic neurotransmission has been implicated in the aetiology of ethanol tolerance and dependence. Cellular expression of the serotonin transporter and serotonin reuptake is modulated via a polymorphic, repetitive element in the 5'-flanking regulatory region of the serotonin transporter gene (5-HTTLPR). We report the association of the low-activity, short variant of the 5-HTTLPR with high ethanol tolerance among young adults in a case-control association study (n = 713). The low-activity 5-HTTLPR showed a significantly increased allele frequency (chi2 = 7.30; df = 2; P = 0.007) and genotype frequency among young adults (< or =26 years) with high ethanol tolerance homozygous for the short allele (chi2 = 7.58; df = 1; P = 0.02). The estimated odds ratio for the homozygous short variant compared to the homozygous long variant was 2.82 (95% CI 1.30-6.11). This indicates that the low-activity 5-HTTLPR may be involved in the neuronal mechanisms responsible for ethanol tolerance and dependence.
Türker
T
T
Institute of Forensic Medicine, University of Giessen, Germany.
Sodmann
R
R
Goebel
U
U
Jatzke
S
S
Knapp
M
M
Lesch
K P
KP
Schuster
R
R
Schütz
H
H
Weiler
G
G
Stöber
G
G
D000328:Adult; D000437:Alcoholism / Q000235:genetics; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics*; D016022:Case-Control Studies; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012701:Serotonin / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D000431:Ethanol