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Chunk #26 — DISCUSSION

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Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts.
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The role of methylation of the OPRM1 gene promoter has been studied by Simon in human cell lines (Andria et al, 1999). SH-SY5Y cells, a neural-derived cell line expressing OPRM1, had low basal OPRM1 promoter methylation. In contrast, two other neural-derived cells lines (IMR-32 and nMB cells), which do not naturally express OPRM1, had high methylation of the OPRM1 promoter. Non-OPRM1 expressing, non-neuronally-derived cell lines (HEK 293, HepG2, and FS-4) had intermediate methylation. Furthermore, transient transfection experiments indicated that methylation might play a role in OPRM1 expression (Andria et al, 1999). It will be of interest, in future studies, to examine the correlation of the level of OPRM1 expression in the lymphocytes with methylation of CpG sites in the promoter region. In addition, studies should be conducted on the role of Sp1 in the regulation of transcription of unmethylated versus methylated OPRM1 genes.