Chunk #9 — 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry
Variations in the μ-opioid receptor (OPRM1) gene and response to NTX are among the most commonly investigated pharmacogenetic effects in research on AUDs. The majority of pharmacogenetics research in AUDs has been conducted in individuals of European ancestry, and these studies have largely focused on the A118G SNP of the μ-opioid receptor. The A118G SNP encodes the substitution of aspartic acid for asparagine (Asn40Asp) with some studies suggesting that G allele (Asp40) carriers3 have a greater response to hedonic and stimulating effects of alcohol,21, 22 make more requests for alcohol during self-administration, and subsequently achieve higher peak breath alcohol concentrations (BrACs).23 While evidence for the association of the A118G SNP and AUD risk has been mixed,24–26 a recent meta-analysis that included over 28,000 participants of European ancestry suggested that the G allele provided a moderate protective effect against the development of substance dependence,27 although a different meta-analysis indicated that G allele carriers of Asian ancestry were at increased risk for developing an AUD.28 Differences in the relationship between A118G allele type and AUD risk across ancestries could necessitate tailoring pharmacologic treatments to individuals who carry alleles that result in the best response to the specific treatment in question.
