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Chunk #9 — The mu opioid receptor gene (OPRM1)

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The genetics of the opioid system and specific drug addictions.
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Only two SNPs out of the variants described in dbSNP in the OPRM1 coding sequence (17C>T (Ala6Val) and 118A>G (Asp40Asn) in exon 1) are relatively common at least in one population (see sections below). Numerous SNPs have been described in the regulatory region, some of which are population-specific (Hoehe et al. 2000; Ono et al. 2009b), and several have been functionally characterized. Two promoter polymorphisms, -554G>A and -1320A>G, have been shown to affect transcription (Bayerer et al. 2007). SNPs -554G>A, in a STAT6 binding site, and SNP -995C>A, in a nuclear factor (NF)-kB binding site, decreased the amount of transcription factor binding and the transcriptional activity (Kraus et al. 2001; Kraus et al. 2003). SNP -1793T>A is located in an YY1 transcription binding site; SNP -1699insT is located in an AP-1 binding site (Hoehe et al. 2000). The Poly (ADP-ribose) polymerase-1 (PARP-1) was shown to preferentially bind to the -172T allele and positively regulate OPRM1 gene expression (Ono et al. 2009a). Bioinformatics assessment suggests that C/EBP or CREB binds to the SNP -1748G>A region, OCT-1 binds to the SNP -1565T>C