Polymorphisms of the D4 dopamine receptor alleles in chronic alcoholism.

We have screened genomic DNA for the identification of D4 dopamine receptor polymorphisms. We show that the D4 dopamine receptor genotype in 72 severely affected chronic alcoholics is heterogeneous, with individuals homozygous and heterozygous for the various D4 receptor alleles. Alcoholics demonstrated a greater prevalence of the D4(3) (p < 0.005) and D4(6) (p < 0.005) alleles than has been reported in normals. There was a high prevalence of nicotine abuse among all D4 genotypes. The frequency of other drug abuse was higher in the D4(3,3) and the D4(4,7) groups, and the family history was strongly positive in the D4(2,4) group. The distribution of the D2 alleles showed equivalence in all D4 genotypes, except in D4(4,6) and D4(4,7) in whom the prevalence of the D2 A1A2 allele was 2-fold higher. The polymorphic variations of the D4 receptor genes should be among the factors considered in the assessment of individual differences in susceptibility to disorders such as alcohol abuse or drug addiction that may be mediated through central dopaminergic systems.