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


CONCLUSIONS
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.
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. tbb@ctri.medicine.wisc.edu
Timothy B
TB
Baker
Robert B
RB
Weiss
Daniel
D
Bolt
Andrew
A
von Niederhausern
Michael C
MC
Fiore
Diane M
DM
Dunn
Megan E
ME
Piper
Nori
N
Matsunami
Stevens S
SS
Smith
Hilary
H
Coon
William M
WM
McMahon
Mary B
MB
Scholand
Nanda
N
Singh
John R
JR
Hoidal
Su-Young
SY
Kim
Mark F
MF
Leppert
Dale S
DS
Cannon
D000328:Adult; D000368:Aged; D016739:Behavior, Addictive / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*; D014589:Utah; D014922:Wisconsin
D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human