Background: The A1 allele of the TaqIA polymorphism (rs1800497) in the dopamine D2 receptor gene (DRD2) has been associated with substance use. It is unclear whether this allele is a marker for an underlying propensity for specifically developing a substance use disorder, or more generally to developing an externalizing psychiatric disorder highly correlated with substance use. It is also possible that DRD2 is related to a behavioral phenotype common to externalizing disorders and substance use.
Method: Data was obtained from 104 psychiatrically hospitalized adolescents in a larger assessment study. Adolescents were genotyped for the DRD2 TaqIA site, grouped as carriers of the A1 allele (A1+) or homozygous for the A2 allelle (A1-). Associations of the presence of the A1 allele with externalizing disorders, the intermediate phenotype of impulsivity, and measures of alcohol and drug use were examined.
Results: A diagnosis of conduct disorder and impulsive behavior were both associated with severity of problem drinking and/or drug use. Further, interaction effects were found between the DRD2 TaqIA polymorphism and conduct disorder (trend level) as well as A1+ status and impulsivity, such that adolescents who were carriers of the A1 allele, and had conduct disorder or impulsive behavior, reported higher levels of problematic alcohol use than those who were non-carriers (A2/A2 or A1-). The same interaction effect between this polymorphism and impulsivity was found for severity of problem drug use. In contrast, no interaction effects were found between the DRD2 allele status and ADHD on severity of problem drinking or drug use.
Discussion: These results suggest that the well documented relationship between conduct disorder, the behavioral phenotype of impulsivity, and problematic alcohol/drug use among adolescents may be moderated by A1 carrier status of the DRD2 gene.