In human populations, a commonly investigated SNP (rs1799971) occurs in exon 1 of the μ-opioid receptor gene (OPRM1), in which an adenine to guanine substitution (A118G) exchanges an asparagine for an aspartic acid at a putative N-glycosylation site (N40D). It is common in persons of European (15–30%) and Asian ancestry (40–50%), with lower prevalence in African American and Hispanic populations (1-3%) (Bergen et al., 1997; Gelernter et al., 1999; Tan et al., 2003). Despite the vast number of papers investigating the role of this SNP in human disease and drug responses, a consensus has yet to be reached on its functional consequences. The A118G SNP has been implicated in a wide variety of disorders, such as drug addiction and stress responsivity, and in treatment responses, including dependence and pain reduction; however, the mechanisms that mediate these alterations have not been determined. In this manuscript, we will review the relevant literature investigating the role of this SNP in human disease and treatment response, molecular and cellular function, and animal models that may help explain these effects. Indeed, several comprehensive reviews describe
