OPRM1, which codes for the G protein--coupled mu opioid receptor, is the primary site of action of most opioids. A nonsynonymous SNP in exon 1 of OPRM1, A118G, is the most commonly studied variant for opioid dependence, but its association is controversial. Several studies have reported a positive association between variants in OPRM1 and opiate (including heroin) dependence (11, 20, 81, 120), whereas other studies did not detect an association (101, 138). A study using sensory neurons isolated from a humanized mouse model showed that the A118G missense variant of OPRM1 modulates the morphine and fentanyl pharmacological profile (89). Morphine is approximately fivefold less potent and 26% less efficacious in neurons with the 118GG genotype than it is in neurons with the 118AA genotype. However, there is no difference in the potency and efficacy of the agonist fentanyl in neurons with different genotypes.
