Polymorphisms in the dopamine transporter gene (SLC6A3/DAT1) and alcohol dependence in humans: a systematic review

Pharmacogenomics. 2009 May;10(5):853-66. doi: 10.2217/pgs.09.24.

Abstract

Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic neurotransmission, making the gene encoding the transporter (SLC6A3/DAT1) an attractive candidate in clinical studies on alcohol dependence. We conducted a systematic review of 18 studies examining associations between polymorphisms in DAT1 and alcohol dependence. The DAT1 variable number tandem repeat, the most frequent studied polymorphism in DAT1, did not show a direct association with alcohol dependence in general. Several, but not all, studies found that the DAT1 variable number tandem repeat (9-repeat allele) was associated with alcohol-withdrawal symptoms, such as seizures and delirium tremens. We discuss shortcomings, such as lack of power and disregarding moderating variables, as well as future challenges of gene association studies.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Alcohol Withdrawal Delirium / genetics*
  • Alcoholism / epidemiology
  • Alcoholism / genetics*
  • Alcoholism / metabolism
  • Case-Control Studies
  • DNA, Complementary / genetics
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Environment
  • Family
  • Female
  • Genetic Variation
  • Humans
  • Male
  • Minisatellite Repeats / genetics
  • Racial Groups / genetics
  • Risk Factors
  • Sex Characteristics
  • Tandem Repeat Sequences

Substances

  • DNA, Complementary
  • Dopamine Plasma Membrane Transport Proteins
  • SLC6A3 protein, human