A finding of particular interest in this study corroborated our earlier study using the 10K GeneChip with Caucasians only (Nielsen et al., 2008b). Different variants in the two studies implicate the metabotropic glutamate receptor 8 gene GRM8 in the vulnerability to develop heroin addiction. In the earlier study, variant rs1034576, located 15,742 nucleotides downstream from GRM8, had the second smallest P value for the candidate genes. In our current study, this variant had the 339th smallest P value. In the Caucasians in our current study, variant rs6467108 (not on the 10K GeneChip) had the smallest P value of the candidate genes and is located in an intron of GRM8. Binding of glutamate to mGluR8 inhibits cAMP production and mGluR8 has been suggested to be a presynaptic receptor that modulates glutamate release (Scherer et al., 1997). Glutamate neurotransmission in the ventral tegmental area and in the nucleus accumbens core were shown to be required for heroin seeking and reinforcement in rodents (Xi and Stein, 2002, LaLumiere and Kalivas, 2008). Variants in GRM8 were found to be associated with schizophrenia in Japanese (Takaki et al., 2004).
