The proximal promoter region does not necessarily contain all elements required for tissue-specific gene expression, and regulatory elements can be located great distances from the gene they regulate.14, 24 Only a few potential OPRM1 regulatory variants have been functionally characterized. SNP −554G>A decreased OPRM1 activity in a neuroblastoma cell line, and SNP −1320A>G showed increased OPRM1 activity.22, 25 Association studies of potential regulatory OPRM1 variants with substance dependence were limited to the proximal regulatory region. An association with substance dependence was shown with SNPs −1793T>A, −1699insT, and −2044C>A.26, 27
