Allelic Association of the D2 Dopamine Receptor Gene With Receptor-Binding Characteristics in Alcoholism or Gene ism

Ernest P. Noble, Kenneth Blum, Terry Ritchie, Anne Montgomery, Peter J. Sheridan

Research output: Contribution to journalArticlepeer-review

550 Scopus citations

Abstract

• The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and nonalcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (XhD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd [binding affinity] and Bmax [number of binding sites]) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

Original languageEnglish (US)
Pages (from-to)648-654
Number of pages7
JournalArchives of General Psychiatry
Volume48
Issue number7
DOIs
StatePublished - Jul 1991

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Allelic Association of the D2 Dopamine Receptor Gene With Receptor-Binding Characteristics in Alcoholism or Gene ism'. Together they form a unique fingerprint.

Cite this