Department of Public Health, University of Helsinki, Finland.
Hum Mol Genet. 2009 Oct 15;18(20):4007-12. doi: 10.1093/hmg/ddp322. Epub 2009 Jul 23.
A cluster of three nicotinic acetylcholine receptor genes on chromosome 15 (CHRNA5/CHRNA3/CHRNB4) has been shown to be associated with nicotine dependence and smoking quantity. The aim of this study was to clarify whether the variation at this locus regulates nicotine intake among smokers by using the level of a metabolite of nicotine, cotinine, as an outcome. The number of cigarettes smoked per day (CPD) and immune-reactive serum cotinine level were determined in 516 daily smokers (age 30-75 years, 303 males) from the population-based Health2000 study. Association of 21 SNPs from a 100 kb region of chromosome 15 with cotinine and CPD was examined. SNP rs1051730 showed the strongest association to both measures. However, this SNP accounted for nearly a five-fold larger proportion of variance in cotinine levels than in CPD (R(2) 4.3% versus 0.9%). The effect size of the SNP was 0.30 for cotinine level, whereas it was 0.13 for CPD. Variation at CHRNA5/CHRNA3/CHRNB4 cluster influences nicotine level, measured as cotinine, more strongly than smoking quantity, measured by CPD, and appears thus to be involved in regulation of nicotine levels among smokers.
位于 15 号染色体上的三个烟碱型乙酰胆碱受体基因簇（CHRNA5/CHRNA3/CHRNB4）与尼古丁依赖和吸烟量有关。本研究旨在通过使用尼古丁代谢产物可替宁的水平作为结果，阐明该基因座的变异是否调节吸烟者的尼古丁摄入量。本研究共纳入了来自基于人群的 Health2000 研究的 516 名每日吸烟者（年龄 30-75 岁，303 名男性），并测定了他们每日吸烟量（CPD）和免疫反应性血清可替宁水平。对 15 号染色体上 100 kb 区域的 21 个 SNP 与可替宁和 CPD 的相关性进行了分析。SNP rs1051730 与两种指标的相关性最强。然而，该 SNP 对可替宁水平的变异解释度（R(2)为 4.3%）几乎是对 CPD 变异解释度（R(2)为 0.9%）的五倍。该 SNP 对可替宁水平的效应大小为 0.30，而对 CPD 的效应大小为 0.13。CHRNA5/CHRNA3/CHRNB4 基因簇的变异对尼古丁水平（以可替宁测量）的影响比吸烟量（以 CPD 测量）更强，这表明其可能参与了吸烟者的尼古丁水平调节。
