Alcoholism and Alleles of the Human D2 Dopamine Receptor Locus

TLDR

The association of the A1 allele with alcoholism may reflect chance variation or a modifying effect increasing severity. The study examined whether the A1 allele of the D2 dopamine receptor gene is associated with alcoholism by comparing 32 alcoholics to 25 controls and analyzing 17 nuclear families. All subjects underwent structured psychiatric interviews, clinical assessment, and independent genotyping. The A1 allele was present in 41 % of alcoholics versus 12 % of controls, was significantly associated only in severely ill cases, and showed no linkage or cosegregation in family pedigrees. Further study of the role of the D2 receptor gene in alcoholism is warranted.

Abstract

The association of the A1 allele of the D2 dopamine receptor gene with alcoholism was examined by comparing 32 unrelated white alcoholics with 25 unrelated white controls and by analysis of 17 nuclear families in multigenerational pedigrees of alcoholics in whom the A1 allele was segregating. All subjects had structured psychiatric interviews. Clinical assessment and genotyping were carried out independently. Thirteen (41%) of the 32 alcoholics carried the A1 allele compared with three (12%) of the 25 controls. The association with the A1 allele was significant when controls were compared with a subset of 10 alcoholics with severe medical problems (60% vs 12%), but not less severe cases. However, regardless of clinical severity or subtype, there was no evidence of linkage or cosegregation of the A1 allele and increased susceptibility to alcoholism in informative pedigrees. The possible association in the general population without linkage in families may be explained either by chance variation in our small samples or a modifying effect of the A1 allele that increases severity. Further study of the role of the D2 receptor gene in alcoholism is warranted.