Catechol-O-methyltransferase (COMT) gene variants predict response to bupropion therapy for tobacco dependence.
BACKGROUND
Although bupropion is efficacious for smoking cessation, only a minority of smokers are able to quit. Pharmacogenetic research may improve treatment outcomes through discovery of DNA sequences predictive of successful pharmacotherapy for subgroups of smokers. We investigated variants in the catechol-O-methyltransferase (COMT) gene in a smoking cessation trial of bupropion.


METHODS
A double-blind, placebo-controlled, 10-week trial of bupropion and counseling (with a 6-month follow-up period) was conducted at two university-based smoking cessation research programs. Abstinence was biochemically verified at the end of treatment and at 6 months after the target quit date.


RESULTS
At the end of the treatment phase, statistically significant interaction effects indicated that COMT haplotypes of two SNPs (rs737865 and rs165599) predicted the efficacy of bupropion compared with placebo. This interaction effect was attenuated at 6-month follow-up.


CONCLUSIONS
COMT haplotypes at rs737865 and rs165599 may predict a favorable outcome for bupropion treatment for smoking cessation. European-American smokers with a G allele at both SNPs may not benefit from bupropion treatment. Small numbers of some COMT haplotypes limit interpretation of response. If study findings are confirmed in additional large studies, COMT genotyping could be applied to identify likely responders to bupropion treatment for smoking cessation.
Berrettini
Wade H
WH
Department of Psychiatry, Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA. wadeb@mail.med.upenn.edu
Wileyto
E Paul
EP
Epstein
Leonard
L
Restine
Stephanie
S
Hawk
Larry
L
Shields
Peter
P
Niaura
Ray
R
Lerman
Caryn
C
D000328:Adult; D016642:Bupropion / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D016009:Chi-Square Distribution; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D016896:Treatment Outcome
D018765:Dopamine Uptake Inhibitors; D016642:Bupropion; D002394:Catechol O-Methyltransferase