Dopamine receptor genes (DRD2, DRD3 and DRD4) and gene-gene interactions associated with smoking-related behaviors.
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.
Vandenbergh
David J
DJ
Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA 16802-2321, USA.
O'Connor
Richard J
RJ
Grant
Michael D
MD
Jefferson
Akilah L
AL
Vogler
George P
GP
Strasser
Andrew A
AA
Kozlowski
Lynn T
LT
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects; D010641:Phenotype; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000235:genetics; D020080:Tandem Repeat Sequences / Q000235:genetics; D014029:Tobacco Use Disorder / Q000235:genetics*
D005819:Genetic Markers; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D009538:Nicotine