Dopamine receptor genes (DRD2, DRD3 and DRD4) and gene-gene interactions associated with smoking-related behaviors

Addict Biol. 2007 Mar;12(1):106-16. doi: 10.1111/j.1369-1600.2007.00054.x.


Cigarette smoking, like many addictive behaviors, has a genetic component, and the dopamine D2-like receptor genes (DRD2, DRD3 and DRD4) are candidates for contributing to these behaviors. Phenotypic information concerning smoking-related behaviors from a nationally representative sample of research volunteers was analyzed for association with polymorphisms in these genes. Genotype status at the DRD2 intron 2 simple tandem repeat was related to cigarettes per day (P = 0.035) and heaviness of smoking index (P = 0.049). The presence of the glycine allele at the S9G polymorphism of the DRD3 gene was associated with frequency/quantity measures of smoking [log-transformed time to first cigarette (P = 0.031) and heaviness of smoking index (P = 0.035)]. There was a trend for DRD4 long alleles of the variable number of tandem repeats polymorphism to be associated with reduced severity of three withdrawal symptoms [desire/craving (P = 0.054); anger/irritability (P = 0.10); and trouble sleeping (P = 0.068)]. Interactions between genotypes at all three genes were associated with nervousness (P = 0.020) and trouble sleeping (P = 0.015). An interaction between DRD2 and DRD3 was found for trouble concentrating (P = 0.020). These relationships present possible dopamine-related responses to nicotine that warrant further study.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Female
  • Gene Frequency / genetics
  • Genetic Markers / genetics
  • Humans
  • Introns / genetics
  • Male
  • Middle Aged
  • Nicotine / adverse effects
  • Phenotype*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D3 / genetics*
  • Receptors, Dopamine D4 / genetics*
  • Smoking / genetics*
  • Substance Withdrawal Syndrome / genetics
  • Tandem Repeat Sequences / genetics
  • Tobacco Use Disorder / genetics*


  • Genetic Markers
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Dopamine D4
  • Nicotine