Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15
Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15
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DOI：
10.1093/hmg/ddp322
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发表时间：
2009-10-15
影响因子：
3.5
通讯作者：
Kaprio, Jaakko
中科院分区：
文献类型：
--
作者：
Keskitalo, Kaisu;Broms, Ulla;Kaprio, Jaakko
研究表明，15号染色体上的三个烟碱乙酰胆碱受体基因簇（CHRNA 5/CHRNA 3/CHRNB 4）与尼古丁依赖和吸烟量相关。本研究的目的是通过使用尼古丁代谢产物可替宁的水平作为结果来澄清该位点的变异是否调节吸烟者的尼古丁摄入量。在基于人群的Health 2000研究中，测定了516名每日吸烟者（年龄30-75岁，303名男性）的每日吸烟量（CPD）和免疫反应性血清可替宁水平。研究了来自15号染色体100 kb区域的21个SNP与可替宁和CPD的关联。SNP rs 1051730与这两项指标的相关性最强。然而，该SNP占可替宁水平方差的比例比CPD高近5倍（R-2 4.3%对0.9%）。SNP的效应大小对于可替宁水平为0.30，而对于CPD为0.13。CHRNA 5/CHRNA 3/CHRNB 4簇的变化影响尼古丁水平（测量为可替宁）比吸烟量（测量为CPD）更强，因此似乎参与吸烟者中尼古丁水平的调节。
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.