High ethanol tolerance in young adults is associated with the low-activity variant of the promoter of the human serotonin transporter gene

Neurosci Lett. 1998 Jun 5;248(3):147-50. doi: 10.1016/s0304-3940(98)00347-4.


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.

MeSH terms

  • Adult
  • Alcoholism / genetics
  • Carrier Proteins / drug effects*
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Drug Tolerance
  • Ethanol / pharmacology*
  • Female
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / drug effects*
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins / genetics*
  • Promoter Regions, Genetic / drug effects*
  • Serotonin / genetics*
  • Serotonin Plasma Membrane Transport Proteins


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Ethanol