As one of the few non-synonymous SNPs in OPRM1, the vast majority of pharmacogenetic studies of pain management and OPRM1 have focused on the A118G variant (Table 1). Patients carrying the G allele have been found to require more medication to achieve analgesia when treated with fentanyl, morphine, or morphine-6-glucoronide (M6G) for a variety of pain sources, including surgery and chemotherapy [19-24]. In another trial, the A118G variant was associated with morphine analgesia only in the presence of a two minor alleles at the rs4680 locus located in the COMT gene [25]. Lö tsch et al. also found a trend towards significance towards decreased analgesia in G carriers treated with morphine in an outpatient setting [26]. The reduction in analgesia in carriers of the G allele has also been reported in trials of oxycodone, tramadol, and alfentanil [27-29]. A number of other studies have found the effect of the G allele to be recessive, with G/G individuals requiring more morphine or fentanyl to achieve analgesia [30-34]. The potentially contradictory findings of both dominant and recessive effects for A118G may be
