D2 DOPAMINE RECEPTOR TaqI ALLELES IN MEDICALLY ILL ALCOHOLIC AND NONALCOHOLIC PATIENTS

The prevalence of TaqI A alleles of the D₂ dopamine receptor(DRD2) gene was examined in two subgroups of medically ill nonalcoholics(more prevalent and less prevalent substance users, MPSU andLPSU, respectively) and in two subgroups of medically ill alcoholics(more severe and less severe alcoholics, MSA and LSA, respectively).The prevalence of the Al allele in the 80 nonalcoholic and 73alcoholic patients was 30.0% and 52.1%, respectively (P = 0.009).In the four subgroups of these patients, the prevalence of thisallele was: LPSU = 18.2%, MPSU = 34.5%, LSA = 44.4% and MSA= 58.3%. Linear trend analysis showed that as the use of substancesand severity of alcoholism increase, so does Al prevalence (P= 0.001). Specific, subgroup comparisons showed Al prevalencein MSA to be about 3-fold (P = 0.007) and 1.5-fold (P = 0.04)higher than in LPSU and MPSU subgroups, respectively. Similarly,in a combined analysis of independent studies, Al prevalencein MSA was higher when compared to LSA (P < 5 x 10^–3),MPSU (P < l0^–4 and LPSU (P < l0^–8) subgroups.There was virtually no difference in the prevalence of the Alallele between LSA and MPSU subgroups. None of the specificmedical or neuropsychiatric complications of alcoholism wasassociated with the Al allele. In conclusion, the severity ofalcohol dependence in alcoholics and of substance use behaviorsin controls are important variables in DRD2 allelic association.The present report and converging lines of evidence suggestthat the DRD2 locus could represent a prominent gene risk factorfor susceptibility to severe alcoholism. However, other genesand environmental factors, when combined, still play the largerrole.