The most frequently studied OPRM1 variant is the single nucleotide polymorphism (SNP) A118G (recently renamed 304A/G10) in exon 1 that causes an Asn40Asp substitution2 at a putative glycosylation site in the extracellular domain and occurs at an allelic frequency of between 10% and 40% depending on ethnicity. Numerous case-control association studies have attempted to identify underlying neurobiological correlates between the A118G variant and the risk of opioid dependence, but so far have provided contradictory results. Studies have identified a significant positive correlation between A118G and heroin addiction,8 and an increased affinity for endogenous opioids, particularly beta-endorphin, and agonist-induced activation in vitro.2,4 In contrast, opposite and null findings have also been reported.11,12 Thus, an association between A118G and the risk of opioid dependence has neither been confirmed nor refuted.
