期刊
PHARMACOGENOMICS JOURNAL
卷 14, 期 1, 页码 70-76出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/tpj.2012.50
关键词
CHRNA5 gene; nicotine; rs16969968; smoking topography
资金
- NIH [R21 DA027001, R21 DA024226, R25 CA090314]
A single-nucleotide polymorphism (SNP) in the alpha 5 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 a5 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据