The D2 dopamine receptor gene: a review of association studies in alcoholism

Following our initial observation that the Al allele of the D2 dopamine receptor (DRD2) gene was associated with alcoholism, a number of studies, both in the United States and abroad, have attempted to replicate and extend this finding in different Caucasian populations. In nine independent studies containing a total of 491 heterogeneous alcoholics (less severe and severe) and 495 heterogeneous controls (assessed and unassessed for alcoholism), the prevalence of the Al allele was 43.0% in the former group compared to 25.7% in the latter group (odds ratio = 2.18, p < 10(-7)). The prevalence of the Al allele increased to 56.3% in a more homogeneous sample of 158 severe alcoholics (odds ratio = 3.32, p < 10(-8)). Moreover, the Bl allele of the DRD2 gene was also found to be significantly associated with severe alcoholism. Additional data are accruing which also implicate the DRD2 Al and Bl alleles in substance use disorders other than alcoholism. If further studies continue to support the results currently at hand, they would indicate that the DRD2 gene is the most prominent single gene determinant of susceptibility to severe substance abuse. However, the larger role still appears to be played by a combination of environmental factors and as yet unidentified genes.