Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism

Abstract

Using the dopamine D₂receptor clone λhD2G1, Blum et al recently found that the D₂/<i>Taq</i>I allele (A1) was present in 69% of 35 deceased alcoholics but in only 20% of an equal number of controls. To assess this association further, we evaluated the D₂/Taq I polymorphism and a single-strand conformation polymorphism detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR-SSCP) of the 3' noncoding region of the D₂receptor gene. We studied 40 unrelated white alcoholics, 127 racially matched controls, and two white pedigrees. The Schedule for Affective Disorders and Schizophrenia—Lifetime Version (SADS-L) clinical diagnostic interviews were rated blindly by two clinicians. The SADS-L interviews and other data were then used to ascertain diagnoses according to the<i>Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R)</i>criteria. Alcoholics were subtyped according to age of onset, severity, presence of antisocial personality, and family history. No significant differences in either D₂/<i>Taq</i>I or PCR-SSCP allele frequencies were observed between alcoholics, subpopulations of alcoholics, or controls. The PCR-SSCP polymorphism provided independent information against linkage at the D₂receptor locus. Several recombinants between the D₂/<i>Taq</i>I locus and alcoholism were observed in two white families with an alcoholic parent who possessed the A1 allele. This study does not support a widespread or consistent association between the D₂receptor gene and alcoholism. (<i>JAMA</i>. 1990;264:3156-3160)