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 aeti ology of ethanol tolerance and dependence. Cellular expression of the serotonin transporter and serotonin reuptake is modulated via a polymo rphic, repetitive element in the 5'-flanking regulatory region of the serotonin transporter gene (5-HTTLPR). We report the association of th e low-activity, short variant of the 5-HTTLPR with high ethanol tolera nce among young adults in a case-control association study (n = 713). The low-activity 5-HTTLPR showed a significantly increased allele freq uency (chi(2) = 7.30; df = 2; P = 0.007) and genotype frequency among young adults (less than or equal to 26 years) with high ethanol tolera nce homozygous for the short allele (chi(2) = 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 indicat es that the low-activity 5-HTTLPR may be involved in the neuronal mech anisms responsible for ethanol tolerance and dependence. (C) 1998 Else vier Science Ireland Ltd. All rights reserved