Chunk #11 — 3. Pharmacogenetic Studies of Treatment for Alcohol Use Disorder in Individuals of Diverse Ancestries — 3.1 Individuals of European Ancestry
and NTX compared with medical management and placebo; there was no difference observed between treatment groups in individuals with the Asn40/Asn40 genotype. Furthermore, Asp40 carriers, compared to Asn40Asn40 carriers, had significantly better clinical outcomes when treated with NTX. Interestingly, no significant treatment-by-genotype interactions were observed when participants received MM in combination with combined behavioral intervention (CBI). The authors suggested that this may be due to CBI compensating for the placebo effect by being an intensive and effective intervention that could have precluded NTX-by-gene interactions from being observed.32 While this is a plausible hypothesis, more research is needed to understand why genetic effects may be suppressed when behavioral therapy is also provided. Finally, in addition to the association between the OPRM1 polymorphism and response to NTX, Schacht et al. reported that variation at a variable number tandem repeat (VNTR) polymorphism in the dopamine transporter gene (DAT1/SLC6A3) may moderate NTX and Asp40 allele effects on cue-elicited activation in the ventral striatum and the orbitofrontal cortex, highlighting the importance of these polymorphisms in reward processing.36
