Genetic ancestry as an effect modifier of naltrexone in smoking cessation among African Americans: an analysis of a randomized controlled trial.
OBJECTIVE
To determine whether there were differential quit rates between African Americans (AA) and European Americans with the experimental treatment naltrexone, and examine the role of genetic ancestry on these outcomes among AAs.


METHODS
Data from a previous randomized trial of 315 smokers to naltrexone versus placebo were reanalyzed using West African (WA) genetic ancestry to define subpopulations. Logistic regression models were used to estimate treatment effects on early and end of treatment quit rates, by race and WA ancestry.


RESULTS
Among European Americans (n=136), naltrexone significantly increased quit rates at 4 weeks (62 vs. 43%, P=0.03) with directional, but not statistically significant effects at 12 weeks (30 vs. 18%, P=0.12). In contrast, among the AAs (n=95), quit rates did not differ between naltrexone and placebo groups at either interval (4 weeks: 43 vs. 32%, P=0.27; 12 weeks: 22 vs. 18%, P=0.60). A median split was conducted in AAs for WA ancestry. Among AAs with low WA ancestry, quit rates were significantly higher with naltrexone compared with placebo (60 vs. 27%, P=0.03). There was no advantage in quit rates with naltrexone for the high WA ancestry group.


CONCLUSIONS
Naltrexone efficacy for smoking cessation varies across AA individuals with different levels of WA ancestry. These results suggest that genetic background may partially explain racial differences in drug response.
aDepartment of Pharmacotherapy, University of Utah, Salt Lake City, Utah bDepartment of Surgery, University of Arizona, Tuscon, Arizona cSchool of Public and Environmental Affairs, Indiana University, Bloomington, Indiana dDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas eDepartment of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois, USA.
Adam
A
Bress
Rick
R
Kittles
Coady
C
Wing
Stanley E
SE
Hooker
Andrea
A
King
D000328:Adult; D001741:Black or African American / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D012907:Smoking / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016540:Smoking Cessation; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
D009271:Naltrexone