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

David J. Vandenbergh, Richard J. O'Connor, Michael D. Grant, Akilah L. Jefferson, George P. Vogler, Andrew A. Strasser, Lynn T. Kozlowski

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54 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)106-116
Number of pages11
JournalAddiction Biology
Issue number1
StatePublished - Mar 2007

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health


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