Considering the low frequency of rs1799971, we also evaluated the rs2075572 SNP, which is located in intron 2(53) and has been associated with initiation of smoking.(54) There was not an overall significant association of rs2075572 with heroin abuse, but a greater number of G/G subjects tended to be heroin abusers, while the control group tended to have higher numbers of C/C individuals (Supplementary Table 4). We observed a pronounced genotype-dose effect association of rs2075572 with striatal ELK1 protein levels (F4,46=4.338, p<0.01;Fig. 3B). Heroin carriers of the minor C allele had significantly higher ELK1 levels than heroin subjects homozygous for the G allele (Fig 3B). A similar trend was observed for changes in ELK1 protein expression between control subjects, indicating that individual variation in the OPRM1 gene may result in heterogeneous levels of ELK1. Importantly, the mean value of ELK1 expression for each individual heroin genotype (C/C- 170.8%; C/G- 129.2%; G/G- 106.6%) was higher than the mean value for all control subjects combined (100%).
