Pharmacogenomics of the human μ-opioid receptor

The mu-opioid receptor is a primary target for clinically important opioid analgesics, including morphine, fentanyl and methadone. Many genetic variations have been identified in the human mu-opioid receptor MOP gene (OPRM1), and their implications have been reported in the effects of opioid drugs and susceptibility to drug dependence. Interestingly, agonistic and antagonistic opioid effects are inversely associated with the A118G polymorphism genotype. The A118G polymorphism may also be associated with substance dependence and susceptibility to other disorders, including epilepsy and schizophrenia. The IVS1+A21573G, IVS1-T17286C, and TAA+A5359G polymorphisms in the OPRM1 gene may be associated with alcohol, opioid and tobacco dependence, respectively. However, some studies have failed to confirm the correlations between the polymorphisms and opioid effects and substance dependence. Further studies are needed to elucidate the molecular mechanisms underlying the effects of OPRM1 polymorphisms.