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Nicotine & Tobacco Research Advance Access published online on May 12, 2009
Nicotine & Tobacco Research, doi:10.1093/ntr/ntp064
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Human neuronal acetylcholine receptor A5-A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes

Timothy B. Baker, Robert B. Weiss, Daniel Bolt, Andrew von Niederhausern, Michael C. Fiore, Diane M. Dunn, Megan E. Piper, Nori Matsunami, Stevens S. Smith, Hilary Coon, William M. McMahon, Mary B. Scholand, Nanda Singh, John R. Hoidal, Su-Young Kim, Mark F. Leppert and Dale S. Cannon

Timothy B. Baker, Ph.D., Department of Medicine, Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine, Madison, WI
Robert B. Weiss, Ph.D., Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT
Daniel Bolt, Ph.D., Department of Medicine, Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine, Madison, WI
Andrew von Niederhausern, Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT
Michael C. Fiore, M.D., M.P.H., Department of Medicine, Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine, Madison, WI
Diane M. Dunn, M.D., Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT
Megan E. Piper, Ph.D., Department of Medicine, Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine, Madison, WI
Nori Matsunami, M. D., Ph.D., Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT
Stevens S. Smith, Ph.D., Department of Medicine, Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine, Madison, WI
Hilary Coon, Ph.D., Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT
William M. McMahon, M.D., Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT
Mary B. Scholand, M.D., Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT
Nanda Singh, Ph. D., Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT
John R. Hoidal, M.D., Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah School of Medicine, Salt Lake City, UT
Su-Young Kim, M.S., Department of Medicine, Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine, Madison, WI
Mark F. Leppert, Ph.D., Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT
Dale S. Cannon, Ph.D., Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT

Corresponding Author: Timothy B. Baker, Ph.D., Department of Medicine, Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health, 1930 Monroe Street, Suite 200, Madison, WI 53711, USA. Telephone: 608-262-8673; Fax: 608-265-3102; E-mail: tbb{at}ctri.medicine.wisc.edu


  Abstract

Introduction: Previous research revealed significant associations between haplotypes in the CHRNA5-A3-B4 subunit cluster and scores on the Fagerström Test for Nicotine Dependence among individuals reporting daily smoking by age 17. The present study used subsamples of participants from that study to investigate associations between the CHRNA5-A3-B4 haplotypes and an array of phenotypes not analyzed previously (i.e., withdrawal severity, ability to stop smoking, and specific scales on the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) that reflect loss of control, strong craving, and heavy smoking.

Methods: Two cohorts of current or former smokers (N = 886) provided both self-report data and DNA samples. One sample (Wisconsin) comprised smokers making a quit smoking attempt, which permitted the assessment of withdrawal and relapse during the attempt. The other sample (Utah) comprised participants studied for risk factors for nicotine dependence and chronic obstructive pulmonary disease and included individuals originally recruited in the Lung Health Study.

Results: The CHRNA5-A3-B4 haplotypes were significantly associated with the targeted WISDM-68 scales (Tolerance, Craving, Loss of Control) in both samples of participants but only among individuals who began smoking early in life. The haplotypes were significantly associated with relapse likelihood and withdrawal severity, but these associations showed no evidence of an interaction with age at daily smoking.

Discussion: The CHRNA5-A3-B4 haplotypes are associated with a broad range of nicotine dependence phenotypes, but these associations are not consistently moderated by age at initial smoking.

Received: June 11, 2008; Accepted: October 24, 2008
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