This study demonstrates hypermethylation of two CpG dinucleotide sites in the OPRM1 promoter region in former heroin addicts. Hypermethylation of the −18 and the +204 CpG sites in the former heroin addicts is likely to reduce OPRM1 gene expression since DNA hypermethylation has been shown in other studies to reduce gene expression. When hypermethylated, transcription factor-binding sites have reduced binding affinity for their cognate transcription factors. Since both the −18 and the +204 CpG sites are in potential Sp1 binding sites, the hypermethylation may decrease binding and transactivation by Sp1. Studies on the effect of the hypermethylation at the −18 and +204 CpG sites in the OPRM1 promoter region on transcription binding should be evaluated in future studies.
