Subtracted differential display PCR (SDD) identified NrCAM as a morphine-regulated gene. Sequences that encoded 3’ untranslated regions of NrCAM were among subcloned SDD cDNAs that corresponded to mRNAs whose expression was altered in striata of rats sacrificed 4 hr after treatment with 20 mg/kg morphine. These biochemical results led us to focus on NrCAM. We thus identified 3’ and 5’ blocks of restricted haplotype diversity in NrCAM in European- and Afircan-American samples, and sought association between addiction and allelic frequencies of markers in both of these haplotype blocks. The 3’ haplotype was associated with addiction vulnerability in European American individuals from Samples 1 and 3 (nominal p = 0.0006 and p = 0.003, respectively) and from African-American individuals from Sample 2 (nominal p = 0.0006). However, the phase of the association was opposite in the African-American samples in comparison to the phase in the two European-American samples. Frequencies of the addiction-associated 3’ NrCAM haplotype were thus higher in African American abusers than in controls but lower in two samples of European-American substance abusers than in the corresponding control samples. We
