Human chromosomes 11p15 and 4p12 and alcohol dependence: possible association with the GABRB1 gene.

To determine the role of genes in the chromosomal regions 11p15 and 4p12 in the development of alcohol dependence, a sample of alcoholics (n = 133) and normal controls (n = 89) were screened using polymorphisms in the dopamine D4 receptor (DRD4), tyrosine hydroxylase (TH), and GABA receptor beta1 (GABRbeta1) genes. Comparison of total alcoholics with normal controls for GABRbeta1 gene was highly significant (p = 0.004). The difference between type II alcoholics and normal controls for the same allele frequencies was also significant (p = 0.029). The allele distributions of the polymorphisms in the DRD4 and TH genes in alcoholics and normal controls were similar and their differences were not significant. Our association studies indicate that the GABRbeta1 gene may play a role in the development of alcoholism. Therefore, it is important to screen a sample of well-characterized alcoholics with functional polymorphisms in all of the GABAalpha receptor subunit genes and determine their relationship with alcoholism phenotypes. Results with TH and DRD4 genes indicate that these two genes may not play major roles in the development of alcoholism.