A laboratory-based study of naloxone comparing individuals of European ancestry to those of Asian ancestry found that the effects of the Asn40Asp polymorphism on naloxone-induced HPA-axis activation were restricted to individuals of European ancestry (Hernandez-Avila et al., 2007). A reanalysis of the COMBINE Study data set focusing exclusively on African American participants did not support the efficacy of naltrexone (Ray and Oslin, 2009). However, power to detect this effect was low, increasing the risk of type II error. Moreover, the lack of naltrexone effect might be explained by the low Asp40 allele frequency among African Americans (approximately 7% in the COMBINE Study). Ancestry-specific effects remain a critical area of investigation for naltrexone pharmacogenetics as well as etiological studies. Population genetic issues are not restricted to the Asn40Asp SNP. For example, the Ala6Val polymorphism is more frequent among African Americans (12%) than in individuals of European ancestry (<1%) and Hispanics (3%) (Gelernter et al., 1999). Ethnic differences have been shown to affect haplotype construction for OPRM1 leading to diverse haplotype structures found for a primarily Caucasian sample (Oroszi et al., 2009),
