Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism.
Using the dopamine D2 receptor clone lambda hD2G1, Blum et al recently found that the D2/Taq 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 D2 receptor 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 Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria. Alcoholics were subtyped according to age of onset, severity, presence of antisocial personality, and family history. No significant differences in either D2/Taq 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 D2 receptor locus. Several recombinants between the D2/Taq 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 D2 receptor gene and alcoholism.
Bolos
A M
AM
Section on Genetic Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md 20892.
Dean
M
M
Lucas-Derse
S
S
Ramsburg
M
M
Brown
G L
GL
Goldman
D
D
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000208:ethnology / Q000235:genetics*; D000483:Alleles; D044383:Black People / Q000235:genetics; D015342:DNA Probes; D004277:DNA, Single-Stranded; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2
D015342:DNA Probes; D004277:DNA, Single-Stranded; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2