To assess the potential neurobiological relevance of the two most significantly associated SNPs with heroin abuse in the Caucasian population, we examined the relationship of rs265975 of DRD1 and rs2521985 of DLG4 to their respective striatal gene expression levels. DRD1 mRNA expression differed in the control group depending on genotype such that control subjects homozygous for the C/T genotype of rs265975 had significantly higher levels of DRD1 mRNA expression than C/C individuals (P<0.05, Figure 1A). The genotype dose effect was, however, absent in heroin subjects, showing similar levels irrespective of their DRD1 genotype with mRNA expression lower compared to C/T controls (P<0.01, Figure 1A). For DLG4 mRNA expression, control subjects homozygous for the C/C genotype at rs2521985 had the highest levels of DLG4 mRNA expression as compared to control C/T subjects (P<0.05, Figure 1B) as well as heroin subjects of all genotypes (P<0.01, Figure 1B). Similar to the effects observed for DRD1 genotype in heroin subjects, heroin blunted the normal DLG4 genotype-dependent differences in DLG4 expression apparent in controls (Figure 1B). For both genes, these genotype effects on gene expression were also found in the caudate region of the striatum (data not shown).
