We determined the methylation state of a CpG island in the promoter of the OPRM1 gene in 194 former severe heroin addicts stabilized in methadone maintenance treatment and 135 controls. Two CpG islands are found from 400 nucleotides upstream to 1,000 nucleotides downstream of the transcription start site (Figure 1). The first CpG island, which we studied, is located from nucleotides −93 to 27 (relative to the A of the ATG translation start site). We examined sixteen CpG dinucleotides located at nucleotide −93, −90, −80, −71, −60, −50, −32, −25, −18, −14, −10, +12, +23, +27, +53, and +84 of the OPRM1 gene. The CpG dinucleotides −18 and −14 are located in one potential Sp1 binding site, the +12 CpG site in a second binding site, and the +84 CpG dinucleotide in a third.
