Similarly, genetic variants in the mu-opioid receptor have significant implications in drug addiction. One SNP (118A>G) corresponding to an amino acid change of Asn40Asp in the N-terminus of the receptor is of particular interest. Receptors with this variant have a three-fold greater binding of beta-endorphin, with a corresponding three-fold greater activation of the G-protein coupled inwardly rectifying potassium channels, although no differences in binding or activation by other endogenous opioid peptides nor exogenous opiates were observed (46). In specific cell lines morphine, methadone and DAMGO are all less potent at inhibiting adenylyl cyclase activity for receptors with the Asp40 variant. The Asp40 SNP also lowers receptor levels in expression cell systems compared to the wildtype Asn40 allele, which may be due to differences in glycosylation (46)). The presence of this variant influences the diverse physiological functions under modulation by the mu-opioid receptor, such as stress responsivity and pain perception. Processes related to abnormal stress responsivity, such as alcohol and opioid addictions, were found to be associated with genetic variation at the mu-opioid receptor even though these are very distinct disorders
