The treatment of cell lines with azacitidine has been shown to both up-regulate specific genes and to down-regulate other genes, with the up-regulation predominating (Heller et al. 2008). The latter effect may be due to decreased DNA methylation of these genes, direct inhibition by azacitidine, or to down-regulation of repressors of these genes. Therefore, methylation at the +12 CpG site of the OPRM1 gene may decrease its rate of transcription.