One of the most common variants encoding the mu opioid receptor gene (OPRM1, gene ID 4988,) is a non-synonymous single nucleotide polymorphism (A118G SNP, rs1799971) (Bond et al., 1998). In vitro studies have shown that the minor allele (G) of this SNP is associated with a three-fold increase in binding affinity for the endogenous opioid peptide beta-endorphin (Bond et al., 1998), reduced receptor expression (Zhang et al., 2005), lower level of receptor glycosylation and a reduced receptor half-life (Wang et al., 2012). In vivo human PET imaging studies by our laboratory and others have corroborated the in vitro findings demonstrating that G allele carriers have lower mu-opioid receptor binding than AA homozygotes in alcohol dependent and healthy controls (Weerts et al., 2013), and in smokers and healthy controls (Ray et al., 2011). This SNP has been associated with AUD in some populations (Setiawan et al., 2012), and in some laboratory alcohol administration studies, G allele carriers showed increased subjective responses to alcohol consumption, enhanced reactivity to alcohol cues, and greater sensitivity to naltrexone reducing these effects (Ray and Hutchison, 2004, Ray and Hutchison, 2007, van den Wildenberg et al., 2007)
