The human MOPR gene, OPRM1, [chromosome 6q24-q25] spans over 200kb with at least 9 exons and 19 different splice variants under the control of multiple promoters (Shabalina et al., 2009). The initial receptor subtype, MOPR-1, spanning approximately 80kb and containing 4 exons (http://genome.ucsc.edu), is abundantly expressed and has been most intensely studied. Its haplotype structure includes three large blocks with >100 polymorphisms reported (http://www.hapmap.org). In addition to the exon 1 A118G, there is in vitro functional evidence for only a few of these other polymorphisms. Two promoter polymorphisms, G–554A and A–1320G have been shown to affect transcription: G–554A decreases MOPR transcription but is extremely rare (MAF<0.001) and the A–1320G variant increases transcription, although the exact transcription factor binding to the site is unknown (MAF= 0.21) (Bayerer et al., 2007). In exon 3, G779A (R260H), G794A (R265H), and T802C (S268P) have been shown to decrease receptor coupling and signaling (Befort et al., 2001; Koch et al., 2000; Wang et al., 2001). Other OPRM1 polymorphisms that have been identified and associated with pain or opioid dependence including a short tandem (CA)n repeat
