Associations of nicotine intake measures with CHRN genes in Finnish smokers.
Associations of nicotine intake measures with CHRN genes in Finnish smokers.
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芬兰吸烟者尼古丁摄入量与 CHRN 基因的关联。
DOI：
10.1093/ntr/ntr059
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Kaprio,Jaakko
中科院分区：
文献类型：
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作者：
Keskitalo-Vuokko,Kaisu;Pitkäniemi,Janne;Broms,Ulla;Heliövaara,Markku;Aromaa,Arpo;Perola,Markus;Ripatti,Samuli;Salminen,Outi;Salomaa,Veikko;Loukola,Anu;Kaprio,Jaakko
遗传效应导致吸烟行为的个体差异。尽管已知有害健康的影响，但吸烟的持续性主要是由尼古丁成瘾引起的。由于尼古丁的生理效应是由烟碱乙酰胆碱受体（nAChRs）介导的，我们的目的是检查是否存在于nAChR亚基（CHRN）基因中的单核苷酸多态性（SNP），而不是CHRNA 3/CHRNA 5/CHRNB 4基因簇，与吸烟量或血清可替宁水平有关。（年龄30-75岁，59%男性）评估每天吸烟的数量（CPD）和血清可替宁水平。我们首先研究了位于选定的nAChR亚基基因（CHRNA 2，CHRNA 4，CHRNA 6/CHRNB 3，CHRNA 7，CHRNA 9，CHRNA 10，CHRNB 2，CHRNG/CHRND）上的SNP，这些SNP在全基因组关联研究中通过顺序回归进行单SNP和多SNP关联的基因分型。接下来，我们探讨了个人的单倍型协会使用滑动窗口technique.ResultsAt的8个位点的研究，CHRNG/CHRND（chr 2），单核苷酸多态性（rs 1190452），多个SNP，和2-SNP单倍型分析（SNPs rs 4973539-rs 1190452）都表现出统计学显着关联与可替宁水平。中位可替宁水平在2-SNP单倍型之间变化，从220 ng/ml（AA单倍型）至249 ng/ml（AG单倍型）。我们没有观察到显着的关联与CPD.ConclusionsThese结果提供了进一步的证据表明，γ−δ nAChR亚基基因区域与可替宁水平，但不与CPD的数量，说明有用的生物标志物在遗传分析。
IntroductionGenetic effects contribute to individual differences in smoking behavior. Persistence to smoke despite known harmful health effects is mostly driven by nicotine addiction. As the physiological effects of nicotine are mediated by nicotinic acetylcholine receptors (nAChRs), we aimed at examining whether single nucleotide polymorphisms (SNPs) residing in nAChR subunit (CHRN) genes, other thanCHRNA3/CHRNA5/CHRNB4gene cluster previously showing association in our sample, are associated with smoking quantity or serum cotinine levels.MethodsThe study sample consisted of 485 Finnish adult daily smokers (age 30–75 years, 59% men) assessed for the number of cigarettes smoked per day (CPD) and serum cotinine level. We first studied SNPs residing on selected nAChR subunit genes (CHRNA2,CHRNA4,CHRNA6/CHRNB3,CHRNA7,CHRNA9,CHRNA10,CHRNB2,CHRNG/CHRND) genotyped within a genome-wide association study for single SNP and multiple SNP associations by ordinal regression. Next, we explored individual haplotype associations using sliding window technique.ResultsAt one of the 8 loci studied,CHRNG/CHRND(chr2), single SNP (rs1190452), multiple SNP, and 2-SNP haplotype analyses (SNPs rs4973539–rs1190452) all showed statistically significant association with cotinine level. The median cotinine levels varied between the 2-SNP haplotypes from 220 ng/ml (AA haplotype) to 249 ng/ml (AG haplotype). We did not observe significant associations with CPD.ConclusionsThese results provide further evidence that the γ−δ nAChR subunit gene region is associated with cotinine levels but not with the number of CPD, illustrating the usefulness of biomarkers in genetic analyses.