Chunk #24 — 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.2 Individuals of East Asian Ancestry
There is evidence that other opioid receptor antagonists, such as naloxone, moderate cortisol responses differently in Asp40 carriers relative to Asn40 homozygotes.49, 50 Given the relationship between alcohol and activation of the hypothalamic-pituitary-adrenal axis,51 pharmacogenetic studies of naloxone may be another important avenue of investigation in AD individuals, who show altered cortisol response.52 An investigation of 30 healthy individuals (n=6 Asp40 carriers; n=24 Asn40 homozygotes) used a within-subjects design to examine the effect of naloxone or placebo on plasma cortisol and adrenocorticotropin releasing hormone levels. Healthy Asp40 carriers had higher baseline cortisol levels and higher cortisol response to IV naloxone administration than Asn40 homozygotes (p’s < 0.05),50 but a subsequent study found that this effect was limited to individuals of East Asian ancestry (n=6; p < 0.05).49 These findings point to population-specific effects of opioid receptor blockade when examining Asp40 carriers and indicate that individuals of East Asian ancestry may respond differently to pharmacologic treatment, which could result in different clinical outcomes for this population.
