No association between D2 dopamine receptor (DRD2) alleles or haplotypes and cocaine dependence or severity of cocaine dependence in European- and African-Americans

Background: Association studies between marker alleles in the D2 dopamine receptor gene (DRD2) and various psychiatric illnesses have produced conflicting results. Reports of allelic associations were originally made with alcoholism, but were then extended to other psychiatric disorders; there has been a series of positive reports suggesting an association between DRD2 alleles and substance dependence in European-American (EA) subjects. Methods: In an attempt to replicate the reported association between DRD2 alleles, substance dependence, and severity of substance dependence, we studied allele frequencies for three polymorphic DRD2 systems (TaqI "A," "B," and "D") in 96 EA and 77 African-American (AA) cocaine-dependent subjects, and 87 EA and 45 AA control subjects. To increase our power to detect such an association and to better understand any association detected, we also constructed three-locus haplotypes and compared haplotype frequencies. Results: For both the EA and AA samples, there were no significant differences in allele frequency between substance-dependent and control subjects for any of the three DRD2 polymorphic systems studied. There were also no significant differences in haplotype frequency between substance-dependent and control subjects for either EA or AA subjects; and, finally, there were no significant differences in "A" or "B" system allele frequency by severity. There were, however, significant differences between EAs and AAs. Conclusions: Our data do not support an association between DRD2 alleles or haplotypes and cocaine dependence, in EA or AA subjects. Moreover, DRD2 alleles are not associated with severity of cocaine dependence in this sample. Biol Psychiatry 1999;45:340-345 (C) 1999 Society of Biological Psychiatry.