No Association Between Polymorphisms in the Human Dopamine D3 and D4 Receptors Genes and Alcoholism

The human dopamine D₂ receptor gene (DRD₂) has received considerable attention for the past several years as a potential candidate that may affect susceptibility to alcoholism. The association studies that compared the frequencies of alleles of DRD₂ gene between alcoholics and control groups have produced equivocal results. Dopamine D₃ and D₄ receptor genes (DRD₃ and DRD₄) are in the same class as DRD₂ but with different pharmacological properties. We have used relative risk and haplotype relative risk approaches to test associations between alleles of DRD₃ and DRD₄ genes and alcoholism. For relative risk studies 162 probands from multiple incidence alcoholic families have been compared to 89 psychiatrically normal controls. Haplotype relative risk approaches have used 29 alcoholic probands in which both parents were available for genotyping. The Bal I restriction enzyme site in DRD₃ and tandem repeat (VNTR) in DRD₄ genes polymorphisms were used to genotype the above samples. The results of relative risk approaches for both DRD₃ and DRD₄ genes were negative for comparisons of alcoholics and subtypes of alcoholics with normal controls. Haplotype relative risk approaches also were negative for both genes. These results suggest that any role played by these receptors may account for only part of the variation in susceptibility to alcoholism. Am. J. Med. Genet. 74:281–285, 1997. © 1997 Wiley-Liss, Inc.