Genetic Vulnerability to Drug Abuse

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Abstract
• Alcoholics are more likely than nonalcoholics to display theTaqI A1 restriction fragment length polymorphism of the D2dopamine receptor gene, according to four of six studies that examined alcoholics and controls. The current study examines whether the association observed in alcoholism might extend to other addictive substances by examining D2dopamine receptorTaqI A and B restriction fragment length polymorphisms in polysubstance users and controls free of significant substance use. We hypothesized a stronger association for the B1 restriction fragment length polymorphism since it lies closer to dopamine receptor protein coding and 5'regulatory regions. Heavy polysubstance users and subjects withDSM-III-Rpsychoactive substance use diagnoses displayed significantly higherTaqI B1 frequencies than control subjects;TaqI A1 results for these comparisons were less robust. These results are consistent with a role for a D2dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability.