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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
- Source :
- Addiction (Abingdon, England)
- Publication Year :
- 2008
-
Abstract
- Aims 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. Design, setting, participants Case–control association study with a community-based sample, comprising 363 Caucasians and 72 African Americans (203 cases, 232 controls). Measurements Cases had smoked ≥ five cigarettes/day for ≥ 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. Findings 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.
- Subjects :
- Adult
Male
Pathology
medicine.medical_specialty
media_common.quotation_subject
Sensation
Medicine (miscellaneous)
Single-nucleotide polymorphism
Nerve Tissue Proteins
Smoking Prevention
Receptors, Nicotinic
Polymorphism, Single Nucleotide
03 medical and health sciences
0302 clinical medicine
Internal medicine
Medicine
SNP
Humans
030304 developmental biology
media_common
0303 health sciences
biology
business.industry
CHRNA5
Addiction
Smoking
Case-control study
nicotinic alpha-5 receptor subunit
Research Reports
Odds ratio
Tobacco Use Disorder
single nucleotide polymorphisms (SNPs)
chromosome 15
3. Good health
Minor allele frequency
Psychiatry and Mental health
smokers and never-smokers
Case-Control Studies
biology.protein
Female
business
early smoking experiences
030217 neurology & neurosurgery
Case–control design
Biomedical sciences
Subjects
Details
- ISSN :
- 09652140
- Volume :
- 103
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Addiction (Abingdon, England)
- Accession number :
- edsair.doi.dedup.....e411b911d8ddfd1280c9597da0c05535