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

Vandenbergh DJ, O'Connor RJ, Grant MD, Jefferson AL, Vogler GP, Strasser AA, Kozlowski LT
Addict Biol. 2007 12 (1): 106-16

PMID: 17407504 · 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.

MeSH Terms (19)

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

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