DOPAMINE-D(2)RECEPTOR RFLPS, HAPLOTYPES AND THEIR ASSOCIATION WITH SUBSTANCE USE IN BLACK AND CAUCASIAN RESEARCH VOLUNTEERS

Alleles of the dopamine D2 receptor gene are distinguished by polymorp hic A and B TaqI sites approximately 10 kb 3' to the final exon and bo rdering the second exon, respectively. These alleles have been reporte d to be more prevalent in heavy substance users than in control popula tions in several, although not all studies. Meta-analyses of combined data from available work support significant association. Two competin g hypotheses could explain this association: (1) the A1 and B1 RFLPs a re in linkage disequilibrium with a functional allelic determinant tha t in some way influences behavior; (2) the affected subjects are drawn disproportionately from populations stratified on the basis of, for e xample, ethnicity that happen to have higher A1 and B1 RFLP frequencie s. We report here data collected from 616 substance-abusing and contro l individuals that document substantial differences in A1 RFLP frequen cies between white and black Americans, the almost exclusive presence of the A3 RFLP in blacks, and low frequencies of rare A4 and B3 RFLPs. In blacks, neither the A1 nor B1 RFLPs display association with subst ance use, while white individuals display significant association with polysubstance use. When expressed as a percent of the maximum possibl e disequilibrium, both white and black individuals display strong link age disequilibrium between these loci, although blacks display many mo re A1/B2 chromosomes. These racial differences in TaqI RFLP haplotypes underscore the need for caution in interpreting allelic associations when careful matching for ethnicity has not been performed.