The first pharmacogenetic reports of the Asn40Asp SNP were from studies of naloxone, an opioid antagonist often used to provide a pharmacological challenge of the HPA axis. These initial studies have shown that the Asp40 allele was associated with greater cortisol response to opioid receptor blockade, via naloxone (Wand et al., 2002). The effects of this polymorphism on cortisol response to naloxone were independently replicated (Hernandez-Avila et al., 2003) and shortly after, the first report of naltrexone pharmacogenetics was published (Oslin et al., 2003). Oslin and colleagues (2003), in a combined retrospective analysis of 3 distinct clinical trials, showed that the Asn40Asp polymorphism was associated with clinical response to naltrexone among alcohol-dependent patients. Specifically, individuals with at least 1 copy of the Asp40 allele had lower relapse rates and longer time to return to heavy drinking when treated with naltrexone, as compared to Asn40 homozygotes (Oslin et al., 2003). As these findings emerged, influential reviews have highlighted the potential clinical utility of this polymorphism as a pharmacogenetic predictor of response to naltrexone, 1 of only 3 pharmacotherapies approved by the
