Despite the fact that the majority of opioid analgesics and illicit opioids directly target MOR, few studies have consistently found significant associations between OPRM1 polymorphisms and opioid dependence. The most well-replicated finding is the association between the A118G polymorphism and heroin dependence in the Indian population, which has been observed in four separate studies. In three of the studies, the minor G allele conferred increased risk of addiction [50-52]. The fourth study found decreased risk in individuals with the minor allele, although only 20 cases were analyzed [53]. Levran et al. observed a significant association between heroin dependence in European Americans and the combined genotypes of rs510769 in OPRM1 and rs2236861 in OPRD1, the gene encoding the δ-opoid receptor [54]. However, three studies of opioid addicts of European descent failed to find associations for five additional SNPs [55-57]. The negative findings in these analyses may be the result of analyzing only variants in OPRM1, and not OPRD1. The 118G allele was found to be protective against opioid dependence in a cohort of Malaysians, but this finding was not replicated in
