Pharmacogenetics of the -opioid receptor and the treatment of addictions

Evaluation of: Munafò MR, Elliot KM, Murphy MF, Walton RT, Johnstone EC: Association of the µ-opioid receptor gene with smoking cessation. Pharmacogenomics J. (2007) (In Press) [1] .This well-designed study examined short- and long-term outcome data from a large clinical trial comparing nicotine-replacement therapy (NRT) with placebo in order to test the association between the µ-opioid receptor gene and treatment outcomes. In addition to a significant effect of NRT compared with placebo across time periods, analyses revealed a significant genotype × treatment interaction at 12-week follow-up, such that participants who were homozygous for the A allele were more likely to report smoking abstinence in the NRT condition versus placebo compared with carriers of the G allele. These results did not persist after NRT was discontinued, although its temporal contiguity to treatment suggests it is a true pharmacogenetic effect. Importantly, these findings stand in contrast to previous research in the field. Moreover, the study reported provocative interactions between gender and µ-opioid receptor gene status with regard to long-term treatment outcome, and between abstinence and gender with regard to changes in body mass index. Munafò and colleagues' study has a number of strengths and its overall findings underline the complex ways in which genotype, gender and body mass index may interact in smoking-cessation treatment. The significance of these findings is discussed in the context of pharmacogenetics research in the field of substance-use disorders.