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The D2 Dopamine Receptor Taq I B1 Restriction Fragment Length Polymorphism Appears More Frequently in Polysubstance Abusers

Stevens S. Smith, PhD; Bruce F. O'Hara, PhD; Antonio M. Persico, MD; David A. Gorelick, MD, PhD; David B. Newlin, PhD; David Vlahov, PhD; Liza Solomon, DrPH; Roy Pickens, PhD; George R. Uhl, MD, PhD

Arch Gen Psychiatry. 1992;49(9):723-727.

Abstract
• Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction fragment length polymorphism of the D₂ dopamine 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 D₂ dopamine receptor Taq I 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 with DSM-III-R psychoactive substance use diagnoses displayed significantly higher Taq I B1 frequencies than control subjects; Taq I A1 results for these comparisons were less robust. These results are consistent with a role for a D₂ dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability.

Author Affiliations
From the Addiction Research Center, National Institute on Drug Abuse, Bethesda, Md (Drs Smith, O'Hara, Persico, Newlin, Gorelick, Pickens, and Uhl); Department of Psychiatry, University of Maryland (Dr Gorelick) and the Department of Epidemiology, School of Hygiene and Public Health (Drs Vlahov and Solomon), and Departments of Neurology and Neuroscience, School of Medicine, The Johns Hopkins University (Dr Uhl), Baltimore.

Footnotes
Accepted for publication April 2, 1992.

Presented in part at the 53rd Annual Meeting of the Committee on Problems of Drug Dependence, Palm Beach, Fla, June 18, 1991, and at a meeting, "D2 Receptor Alleles in Substance Abuse: Have We Identified a Relevant Gene?", Baltimore, Md, September 19, 1991.

Reprint requests to Laboratory of Molecular Neurobiology, PO Box 5180, Baltimore, MD 21224 (Dr Uhl).

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