Skip Navigation



Human Molecular Genetics Advance Access published online on July 1, 2008
Human Molecular Genetics, doi:10.1093/hmg/ddn181
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
17/18/2834    most recent
ddn181v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Conti, D. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Conti, D. V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nicotinic acetylcholine receptor β2 subunit gene implicated in a systems-based candidate gene study of smoking cessation

David V. Conti1,*, Won Lee1, Dalin Li1, Jinghua Liu1, David Van Den Berg1, Paul D. Thomas2, Andrew W. Bergen3, Gary E. Swan3, Rachel F. Tyndale4, Neal L. Benowitz5, Caryn Lerman6 for the Pharmacogenetics of Nicotine Addiction and Treatment Consortium

1 Department of Preventive Medicine, Keck School of Medicine, Zilkha Neurogenetics Institute, University of Southern California, Los Angeles, CA USA 2 Evolutionary Systems Biology, Artificial Intelligence Center, SRI International, Menlo Park, CA USA 3 Center for Health Sciences, SRI International, Menlo Park, CA USA 4 Centre for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada 5 Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, Department of Medicine, University of California, San Francisco, CA USA 6 Departments of Psychiatry and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA USA

* Corresponding Author: David V. Conti, Ph.D. Department of Preventive Medicine University of Southern California 1501 San Pablo Street ZNI 445 Los Angeles, CA 90089 Tel: 323-442-3140 Fax: 323-442-2448 Email: dconti{at}usc.edu

Received May 13, 2008; Revised June 11, 2008; Accepted June 17, 2008

While the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated, there is substantial variability among individuals in treatment response. We performed a systems-based candidate gene study of 1,295 single nucleotide polymorphisms (SNPs) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a bupropion placebo-controlled randomized clinical trial. Putative functional variants were supplemented with tagSNPs within each gene. We used global tests of main effects and treatment interactions, adjusting the p-values for multiple correlated tests. A SNP (rs2072661) in the 3' UTR region of the β2 nicotinic acetylcholine receptor subunit (CHRNB2) has an impact on abstinence rates at end of treatment (adjusted p = 0.01) and after a 6-month follow-up period (adjusted p = 0.0002). This latter p-value is also significant with adjustment for the number of genes tested. Independent of treatment at 6-month follow-up, individuals carrying the minor allele have substantially decreased odds of quitting (OR = 0.31; 95% CI 0.18–0.55). Effect estimates indicate that treatment is more effective for individuals with the wild-type (OR = 2.14, 95% CI 1.20-3.81) compared to individuals carrying the minor allele (OR = 0.83, 95% CI 0.32-2.19), although this difference is only suggestive (p = 0.10). Furthermore, this SNP demonstrated a role in the time to relapse (p = 0.0002) and an impact on withdrawal symptoms at target quit date (p = 0.0009). Overall, while our results indicate strong evidence for CHRNB2 in ability to quit smoking, these results require replication in an independent sample.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am J EpidemiolHome page
M. Wenten, W. J. Gauderman, K. Berhane, P.-C. Lin, J. Peters, and F. D. Gilliland
Functional Variants in the Catalase and Myeloperoxidase Genes, Ambient Air Pollution, and Respiratory-related School Absences: An Example of Epistasis in Gene-Environment Interactions
Am. J. Epidemiol., November 6, 2009; (2009) kwp310v1.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
K. A. Perkins, C. Lerman, M. Mercincavage, C. A. Fonte, and J. L. Briski
Nicotinic Acetylcholine Receptor {beta}2 Subunit (CHRNB2) Gene and Short-Term Ability to Quit Smoking in Response to Nicotine Patch
Cancer Epidemiol. Biomarkers Prev., October 1, 2009; 18(10): 2608 - 2612.
[Abstract] [Full Text] [PDF]

Home page
 Nicotine Tob ResHome page
T. B. Baker, K. M. Cummings, D. K. Hatsukami, C. A. Johnson, C. Lerman, R. Niaura, and S. S. O'Malley
Transdisciplinary Tobacco Use Research Centers: Research achievements and future implications
Nicotine Tob Res, October 1, 2009; 11(10): 1231 - 1244.
[Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. M. Freathy, S. M. Ring, B. Shields, B. Galobardes, B. Knight, M. N. Weedon, G. D. Smith, T. M. Frayling, and A. T. Hattersley
A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy
Hum. Mol. Genet., August 1, 2009; 18(15): 2922 - 2927.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. V. Breton, H. Vora, M. T. Salam, T. Islam, M. Wenten, W. J. Gauderman, D. Van Den Berg, K. Berhane, J. M. Peters, and F. D. Gilliland
Variation in the GST mu Locus and Tobacco Smoke Exposure as Determinants of Childhood Lung Function
Am. J. Respir. Crit. Care Med., April 1, 2009; 179(7): 601 - 607.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.