D-2-DOPAMINE RECEPTOR TAQI-A ALLELES IN MEDICALLY ILL ALCOHOLIC AND NONALCOHOLIC PATIENTS

The prevalence of TaqI A alleles of the D-2 dopamine receptor (DRD2) g ene was examined in two subgroups of medically ill nonalcoholics (more prevalent and less prevalent substance users, MPSU and LPSU, respecti vely) and in two subgroups of medically ill alcoholics (more severe an d less severe alcoholics, MSA and LSA, respectively). The prevalence o f the A1 allele in the 80 nonalcoholic and 73 alcoholic patients was 3 0.0% and 52.1%, respectively (P = 0.009). In the four subgroups of the se patients, the prevalence of this allele was: LPSU = 18.2%, MPSU = 3 4.5%, LSA = 44% and MSA = 58.3%. Linear trend analysis showed that as the use of substances and severity of alcoholism increase, so does A1 prevalence (P = 0.001). Specific, subgroup comparisons showed A1 preva lence in MSA to be about 3-fold (P = 0.007) and 1.5-fold (P = 0.04) hi gher than in LPSU and MPSU subgroups, respectively. Similarly, in a co mbined analysis of independent studies, A1 prevalence in MSA was highe r when compared to LSA (P < 5 x 10(-3)), MPSU (P < 10(-4)) and LPSU (P < 10(-8)) subgroups. There was virtually no difference in the prevale nce of the A1 allele between LSA and MPSU subgroups. None of the speci fic medical or neuropsychiatric complications of alcoholism was associ ated with the Al allele. In conclusion, the severity of alcohol depend ence in alcoholics and of substance use behaviors in controls are impo rtant variables in DRD2 allelic association. The present report and co nverging lines of evidence suggest that the DRD2 locus could represent a prominent gene risk factor for susceptibility to severe alcoholism. However, other genes and environmental factors, when combined, still play the larger role.