title: Genetic variation in mu-opioid-receptor-interacting proteins and smoking cessation in a nicotine replacement therapy trial.
abstract: Extending a previous finding of an association between functional genetic variation in the mu-opioid receptor gene and response to nicotine replacement therapy, we explored the role of genetic variants in two genes encoding mu-opioid-receptor-interacting proteins, namely ARRB2 and HINT1. Participants were 374 smokers treated for nicotine dependence with either transdermal nicotine or nicotine nasal spray for 8 weeks in an open-label randomized trial. In a logistic regression model controlling for OPRM1 genotype, treatment type, and other covariates, we found no significant main effect of ARRB2 genotype on abstinence at either end of treatment or 6-month follow-up. Participants with the HINT1 TT genotype had significantly higher abstinence rates at 6-month follow-up, but this may not be a pharmacogenetic effect, given that the participants were drug free during this time. Haplotype analysis did not reveal any significant associations for either gene. We found an interaction of ARRB2 and OPRM1 genotype on abstinence at 6 months that approached significance; however, interpretation of this finding is limited by the small number of participants with the minor alleles for both genes. Although these data do not provide support for the role of genetic variation in these mu-opioid-receptor-interacting proteins and smoking cessation, further exploration of opioid pathway genes in larger prospective pharmacogenetic trials may be warranted.
authors.affiliation: Department of Pharmacology, and Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Riju
authors.initials: R
authors.lastname: Ray
authors.forename: Christopher
authors.initials: C
authors.lastname: Jepson
authors.forename: E Paul
authors.initials: EP
authors.lastname: Wileyto
authors.forename: John P
authors.initials: JP
authors.lastname: Dahl
authors.forename: Freda
authors.initials: F
authors.lastname: Patterson
authors.forename: Margaret
authors.initials: M
authors.lastname: Rukstalis
authors.forename: Angela
authors.initials: A
authors.lastname: Pinto
authors.forename: Wade
authors.initials: W
authors.lastname: Berrettini
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
mesh_terms: D000328:Adult; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018722:Nicotinic Agonists; D017450:Receptors, Opioid, mu; D009538:Nicotine