The most common and most studied non-synonymous SNP is rs1799971, more often referred to as A118G, with a global minor allele frequency of 19%. The A118G variant causes an ASP>ASN residue change and occurs more frequently in non-African populations. A number of functional effects have been associated with the A118G polymorphism. The G allele of A118G creates a novel CpG-methylation site, preventing the upregulation of OPRM1 in response to chronic opioid use [3]. Copies of mRNA carrying the variant G allele were shown to be less abundant in human brain tissue than the A allele and studies of stably transfected cell lines have indicated that the A118G variant results in reduced expression of MOR at the cell surface [4, 5]. Decreased accumulation of the second-messenger cAMP transfected cells was observed in the presence of morphine, methadone, and DAMGO [5]. This reduced signaling following DAMGO activation has also been shown in human postmortem brain tissue [6]. In contrast, data suggest that β-endorphin has higher binding affinity and increased signaling at the variant receptor [7].
