The strong interactions of HOMER1 and DRD1 in heroin abusers are intriguing given their neurobiological and chromosomal connections. HOMER1 and DRD1 are located on chromosome 5 (5q14 and 5q35, respectively), raising the possibility of a potential physical interaction between these two genes. Unfortunately, the technical strategies such as chromosome confirmation capture assays are not yet optimized to evaluate such physical interactions in human subjects and await future technological advances. Another rationale to account for the strong interaction between HOMER1 and DRD1 may relate to their neuroanatomical organization. Both proteins are highly expressed in the striatum, neocortex and amygdala, brain regions relevant to various aspects of addiction vulnerability including reward, goal-directed behavior, decision-making and craving. Of these regions, we only detected a significant interaction between rs265973 of DRD1 and HOMER1 levels in the striatum. In fact, without consideration of the DRD1 genotype, one would have concluded a lack of significant difference of HOMER1b/c levels between heroin abusers and controls. Instead, there was a clear inverse relationship as heroin subjects with the T/T genotype at rs265973 of DRD1 had the highest levels
