The non-synonymous variant rs1799971 (118A>G, Asn40Asp) was shown to remove a potential N-glycosylation site in the extracellular domain, to be more potent in beta-endorphin binding and receptor activity, and to reduce receptor signaling efficacy.1 Healthy subjects with the 118G allele showed an increased basal level of cortisol and greater cortisol responses to opioid receptor blockade with naloxone in a population-specific manner.2-4 Several studies reported positive association of the 118G variant with opioid dependence and other substance dependencies, in diverse populations,5-7 while other studies did not detect association.8, 9 The clinical relevance of this polymorphism for opioid analgesia and opioid adverse effects is still debatable.10-12 The 118G allele frequencies varied between populations, with high frequency in Asian populations (0.35-0.48), moderate frequency in European populations (0.1-0.17), and low frequency in African populations (<0.04).13
