Assessment of toxicology in heroin abusers revealed a strong positive correlation between ELK1 protein expression in the putamen and urine concentrations of 6-MAM, the rapid metabolite of heroin (r2=0.70, p<0.05), but this was strongly influenced by one subject (Figure 4A). Interestingly, documentation of drug use history available for some subjects showed that levels of ELK1 mRNA tended to be negatively correlated with age of onset of heroin use for subjects carrying the G allele of rs2075572 (r2=0.37, p<0.05), suggesting elevated ELK1 with long-term heroin use, but this was predominantly driven by those with the G/G genotype (r2=0.95, p<0.01; Fig 4B). Importantly, this subset of G allele heroin abusers was representative of the larger population of subjects as their ELK1 mRNA expression levels (124.00±4.04% of controls, p<0.01; F1,28=10.328, data not shown) were comparable to that in the larger cohort.
