Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation

A. M. Leventhal, S. P. David, M. Brightman, D. Strong, J. E. McGeary, R. A. Brown, E. E. Lloyd-Richardson, M. Munafò, G. R. Uhl, Raymond Niaura

Research output: Contribution to journalArticle

Abstract

Smokers (10 cigarettes per day, N331) of European ancestry taking part in a double-blind placebo-controlled randomized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of tandem repeats polymorphism in exon III of the dopamine D4 receptor gene. Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2, 6 and 12 months after the end of treatment indicated that bupropion (vs placebo) predicted increased odds of abstinence. The main effect of Genotype was not significant. A Genotype × Treatment interaction (P0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR)1.31, P0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR1.06, P0.23). The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates (P0.01) and in analyses predicting continuous abstinence (P's0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches.

Original languageEnglish (US)
Pages (from-to)86-92
Number of pages7
JournalPharmacogenomics Journal
Volume12
Issue number1
DOIs
StatePublished - Feb 2012

Fingerprint

Dopamine D4 Receptors
Bupropion
Smoking Cessation
Genes
Alleles
Genotype
Therapeutics
Placebos
Minisatellite Repeats
Pharmacogenetics
Homozygote
Tobacco Products
Counseling
Exons
Randomized Controlled Trials
Odds Ratio
Demography

Keywords

  • bupropion Introduction
  • DRD4
  • smoking cessation
  • VNTR

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Leventhal, A. M., David, S. P., Brightman, M., Strong, D., McGeary, J. E., Brown, R. A., ... Niaura, R. (2012). Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation. Pharmacogenomics Journal, 12(1), 86-92. https://doi.org/10.1038/tpj.2010.64

Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation. / Leventhal, A. M.; David, S. P.; Brightman, M.; Strong, D.; McGeary, J. E.; Brown, R. A.; Lloyd-Richardson, E. E.; Munafò, M.; Uhl, G. R.; Niaura, Raymond.

In: Pharmacogenomics Journal, Vol. 12, No. 1, 02.2012, p. 86-92.

Research output: Contribution to journalArticle

Leventhal, AM, David, SP, Brightman, M, Strong, D, McGeary, JE, Brown, RA, Lloyd-Richardson, EE, Munafò, M, Uhl, GR & Niaura, R 2012, 'Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation', Pharmacogenomics Journal, vol. 12, no. 1, pp. 86-92. https://doi.org/10.1038/tpj.2010.64
Leventhal, A. M. ; David, S. P. ; Brightman, M. ; Strong, D. ; McGeary, J. E. ; Brown, R. A. ; Lloyd-Richardson, E. E. ; Munafò, M. ; Uhl, G. R. ; Niaura, Raymond. / Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation. In: Pharmacogenomics Journal. 2012 ; Vol. 12, No. 1. pp. 86-92.
@article{7a4f0f7f8b0d42ffbb61e596378f841e,
title = "Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation",
abstract = "Smokers (10 cigarettes per day, N331) of European ancestry taking part in a double-blind placebo-controlled randomized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of tandem repeats polymorphism in exon III of the dopamine D4 receptor gene. Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2, 6 and 12 months after the end of treatment indicated that bupropion (vs placebo) predicted increased odds of abstinence. The main effect of Genotype was not significant. A Genotype × Treatment interaction (P0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR)1.31, P0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR1.06, P0.23). The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates (P0.01) and in analyses predicting continuous abstinence (P's0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches.",
keywords = "bupropion Introduction, DRD4, smoking cessation, VNTR",
author = "Leventhal, {A. M.} and David, {S. P.} and M. Brightman and D. Strong and McGeary, {J. E.} and Brown, {R. A.} and Lloyd-Richardson, {E. E.} and M. Munaf{\`o} and Uhl, {G. R.} and Raymond Niaura",
year = "2012",
month = "2",
doi = "10.1038/tpj.2010.64",
language = "English (US)",
volume = "12",
pages = "86--92",
journal = "Pharmacogenomics Journal",
issn = "1470-269X",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Dopamine D4 receptor gene variation moderates the efficacy of bupropion for smoking cessation

AU - Leventhal, A. M.

AU - David, S. P.

AU - Brightman, M.

AU - Strong, D.

AU - McGeary, J. E.

AU - Brown, R. A.

AU - Lloyd-Richardson, E. E.

AU - Munafò, M.

AU - Uhl, G. R.

AU - Niaura, Raymond

PY - 2012/2

Y1 - 2012/2

N2 - Smokers (10 cigarettes per day, N331) of European ancestry taking part in a double-blind placebo-controlled randomized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of tandem repeats polymorphism in exon III of the dopamine D4 receptor gene. Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2, 6 and 12 months after the end of treatment indicated that bupropion (vs placebo) predicted increased odds of abstinence. The main effect of Genotype was not significant. A Genotype × Treatment interaction (P0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR)1.31, P0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR1.06, P0.23). The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates (P0.01) and in analyses predicting continuous abstinence (P's0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches.

AB - Smokers (10 cigarettes per day, N331) of European ancestry taking part in a double-blind placebo-controlled randomized trial of 12 weeks of treatment with bupropion along with counseling for smoking cessation were genotyped for a variable number of tandem repeats polymorphism in exon III of the dopamine D4 receptor gene. Generalized estimating equations predicting point-prevalence abstinence at end of treatment and 2, 6 and 12 months after the end of treatment indicated that bupropion (vs placebo) predicted increased odds of abstinence. The main effect of Genotype was not significant. A Genotype × Treatment interaction (P0.005) showed that bupropion predicted increased odds of abstinence in long-allele carriers (odds ratios (OR)1.31, P0.0001), whereas bupropion was not associated with abstinence among short-allele homozygotes (OR1.06, P0.23). The Genotype × Treatment interaction remained when controlling for demographic and clinical covariates (P0.01) and in analyses predicting continuous abstinence (P's0.054). Bupropion may be more efficacious for smokers who carry the long allele, which is relevant to personalized pharmacogenetic treatment approaches.

KW - bupropion Introduction

KW - DRD4

KW - smoking cessation

KW - VNTR

UR - http://www.scopus.com/inward/record.url?scp=84856229702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856229702&partnerID=8YFLogxK

U2 - 10.1038/tpj.2010.64

DO - 10.1038/tpj.2010.64

M3 - Article

VL - 12

SP - 86

EP - 92

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

SN - 1470-269X

IS - 1

ER -