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Variation in the α 5 nicotinic acetylcholine receptor subunit gene predicts cigarette smoking intensity as a function of nicotine content.
MedLine Citation:
PMID:  23358500     Owner:  NLM     Status:  Publisher    
A single-nucleotide polymorphism (SNP) in the α5 nicotinic acetylcholine receptor subunit gene, rs16969968, has been repeatedly associated with both smoking and respiratory health phenotypes. However, there remains considerable debate as to whether associations with lung cancer are mediated through effects on smoking behavior. Preclinical studies suggest that α5 receptor subunit expression and function may have a direct role in nicotine titration during self administration. The present study investigated the association of CHRNA5 polymorphisms and smoking topography in 66 smokers asked to smoke four nicotine-containing (nicotine yield=0.60 mg) and four placebo (nicotine yield <0.05 mg) cigarettes, during separate experimental sessions. Genotype at rs16969968 predicted nicotine titration, with homozygotes for the major allele (G:G) displaying significantly reduced puff volume in response to nicotine, whereas minor allele carriers (A:G or A:A) produced equivalent puff volumes for placebo and nicotine cigarettes. The present results suggest that puff volume may be a more powerful objective phenotype of smoking behavior than self-reported cigarettes per day and nicotine dependence. Further, these results suggest that the association between rs16969968 and lung cancer may be mediated by the quantity of smoke inhaled.The Pharmacogenomics Journal advance online publication, 29 January 2013; doi:10.1038/tpj.2012.50.
D A Macqueen; B W Heckman; M D Blank; K Janse Van Rensburg; J Y Park; D J Drobes; D E Evans
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-29
Journal Detail:
Title:  The pharmacogenomics journal     Volume:  -     ISSN:  1473-1150     ISO Abbreviation:  Pharmacogenomics J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083949     Medline TA:  Pharmacogenomics J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
University of South Florida, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
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