Numerous genetic association studies have sought to find variants in OPRM1 that influence the risk for addiction [3, 20, 25, 28, 38–40]. One functional coding variant in OPRM1 is the A118G polymorphism (rs1799971), which eliminates a glycosylation site in the extracellular domain of the protein. This SNP has been associated with heroin and cocaine dependence in several populations [13, 14, 23, 26, 33]. However, two meta-analyses that studied A118G in substance dependent populations did not find an overall significant association with addiction, nor did they find evidence of an association when ethnicity or drug type were analyzed [2, 15]. The C17T (rs1799972) variant in exon 1 of OPRM1 is another putatively functional variant that changes from an alanine to a valine. Association studies have shown rs1799972 to be part of a haplotype associated with cocaine/heroin dependence in African Americans [19] and with quantitative drug abuse scores (KMSK scales) for cocaine, alcohol and tobacco use in African American women [12]. However, negative findings have also been reported [11].
