Brain event-related potentials, dopamine D2 receptor gene polymorphism, and smoking.

This paper explores the relationship between the DRD2 gene polymorphism, P300, and smoking. Both smoking and DRD2 have significant reducing effects on P300 amplitude. The effect of smoking is apparent only in the presence of the A1 allele of the DRD2 locus. Transmission/disequilibrium analyses show a negative association between the A2 allele and smoking initiation, suggesting a protective effect of this allele. When the sample is stratified into lower- and higher-P300 categories, we find a significant association between A1 and current smoking only in individuals with lower P300. Both concordance for smoking and DRD2 genotype are significant predictors of sib-pair similarity in P300 amplitude. These results suggest a synergistic effect of different neurogenetic risk factors contributing to nicotine dependence. Neurocognitive variation (P300) may moderate the association between DRD2 and smoking. Alternatively, DRD2 genotype may modulate the long-term impact of nicotine on neurocognitive functioning.