Given our hypotheses of DRD1 and glutamatergic interactions and to understand the role by which genetic variation may be playing in disease risk, we examined the relationship between the DRD1 rs265973 and HOMER1b/c protein levels in putamen as this was the most significant gene-gene interaction observed (Table 2). The allelic frequencies for rs265973 were similar in this subset and the full population (P=0.23 and 0.73 for controls and heroin subjects, respectively). Although there was not an overall difference between Homer1b/c levels in control and heroin groups (Figure 2A), a differential pattern was observed between rs265973 DRD1 and HOMER1b/c protein levels depending on the disease grouping, such that in control subjects, individuals with the C/C genotype at rs265973 had the highest levels of HOMER1b/c protein expression (Figure 2B). In contrast, individuals with the T/T genotype had the lowest levels of HOMER1b/c protein level (Figure 2B). This dose-dependent pattern was completely reversed in heroin subjects with T/T subjects having the greatest level of HOMER1b/c protein level (P<0.01, Figure 2B). These effects were specific to the striatum since the DRD1 rs265973 was not
