Effects of the serotonin transporter (5-HTTLPR) and α2A-adrenoceptor (C-1291G) genotypes on substance use in children and adolescents: a longitudinal study

Psychopharmacology (Berl). 2011 May;215(1):13-22. doi: 10.1007/s00213-010-2109-z. Epub 2010 Dec 8.


Rationale and objective: Twin studies suggest that substance use initiation in children and adolescents is determined primarily by environmental influences, whereas the establishment of use patterns is strongly controlled by genetic factors. The present study analysed the effects of the serotonin transporter promoter polymorphism [5-HT transporter gene-linked polymorphic region (5-HTTLPR)] and the α(2A)-adrenoceptor C-1291G genotype (ADRA2A C-1291G) as well as their interaction effects on alcohol, tobacco and drug use from preadolescence to the late adolescence.

Methods: Initial sample of 9-year-old children of Estonian Children Personality Behaviour and Health Study (n = 583) was recalled at ages 15 and 18. Participants reported in all waves how frequently they smoked and used alcohol and illicit drugs.

Results: 5-HTTLPR had age-dependent effects on alcohol, tobacco and drug use: substance use did not differ by genotype at age 9, but at age 15, the participants with the short (s)/s genotype had higher tobacco use, and at age 18, they were more active alcohol, drug and tobacco users. Effects of ADRA2A C-1291G on drug use were dependent on gender, age and 5-HTTLPR. Males (age 18) with ADRA2A CG genotype, when compared to other participants, tended to have higher drug use especially when they had s/s genotype of 5-HTTLPR.

Conclusions: Our results reveal that expression of genetic vulnerability for substance use in children and adolescents may depend on age, gender, interaction of genes, and type of substance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Analysis of Variance
  • Child
  • Data Interpretation, Statistical
  • Estonia / epidemiology
  • Female
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Polymorphism, Genetic
  • Receptors, Adrenergic, alpha-2 / genetics*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Sex Factors
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / genetics*
  • Substance-Related Disorders / metabolism


  • ADRA2A protein, human
  • Receptors, Adrenergic, alpha-2
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins