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Chunk #3 — Oxytocin — OXTR Methylation

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Prevention of Early Substance Use Mediates, and Variation at SLC6A4 Moderates, SAAF Intervention Effects on OXTR Methylation.
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One potential mechanism by which SAAF could influence or regulate the oxytocin system, possibly with long-term implications, is through epigenetic effects at OXTR. Methylation of specific CpG sites (i.e., regions of DNA in which cytosine occurs next to guanine separated by only one phosphate bond), can influence access to key regulatory elements controlling the rate of gene transcription, and so influence gene expression and larger systemic effects. Because greater methylation of the first exon is particularly likely to predict lower gene expression (e.g., Brenet et al., 2011), characterizing individual differences in methylation of OXTR in the region of the first exon may be particularly informative, and so provides a useful starting point for examination of potential biomarkers of SAAF’s impact on the oxytonergic system. In keeping with this general expectation, Kusui, Kimura, Ogita, Nakamura, Matsumara, Koyama, … Murata, (2001) found that methylation of the CpG island surrounding the first exon of OXTR has a substantial effect on gene transcription, and that the strongest methylation effects were attributable to methylation of a sub-region around the end of the first exon and extending into the first intron.