Association of a single nucleotide polymorphism in neuronal acetylcholine receptor subunit alpha 5 (CHRNA5) with smoking status and with 'pleasurable buzz' during early experimentation with smoking.
OBJECTIVE
To extend the previously identified association between a single nucleotide polymorphism (SNP) in neuronal acetylcholine receptor subunit alpha-5 (CHRNA5) and nicotine dependence to current smoking and initial smoking-experience phenotypes.


METHODS
Case-control association study with a community-based sample, comprising 363 Caucasians and 72 African Americans (203 cases, 232 controls).


METHODS
Cases had smoked > or = five cigarettes/day for > or = 5 years and had smoked at their current rate for the past 6 months. Controls had smoked between one and 100 cigarettes in their life-time, but never regularly. Participants also rated, retrospectively, pleasurable and displeasurable sensations experienced when they first smoked. We tested for associations between smoking phenotypes and the top 25 SNPs tested for association with nicotine dependence in a previous study.


RESULTS
A non-synonymous coding SNP in CHRNA5, rs16969968, was associated with case status [odds ratio (OR) = 1.5, P = 0.01] and, in Caucasians, with experiencing a pleasurable rush or buzz during the first cigarette (OR = 1.6, P = 0.01); these sensations were associated highly with current smoking (OR = 8.2, P = 0.0001).


CONCLUSIONS
We replicated the observation that the minor allele of rs16969968 affects smoking behavior, and extended these findings to sensitivity to smoking effects upon experimentation. While the ability to test genetic associations was limited by sample size, the polymorphism in the CHRNA5 subunit was shown to be associated significantly with enhanced pleasurable responses to initial cigarettes in regular smokers in an a priori test. The findings suggest that phenotypes related to subjective experiences upon smoking experimentation may mediate the development of nicotine dependence.
Sherva
Richard
R
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Wilhelmsen
Kirk
K
Pomerleau
Cynthia S
CS
Chasse
Scott A
SA
Rice
John P
JP
Snedecor
Sandy M
SM
Bierut
Laura J
LJ
Neuman
Rosalind J
RJ
Pomerleau
Ovide F
OF
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012677:Sensation / Q000187:drug effects*; D012907:Smoking / Q000235:genetics*; D000074606:Smoking Prevention; D014029:Tobacco Use Disorder / Q000235:genetics / Q000523:psychology
C447158:CHRNA5 protein, human; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic
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