Alpha-5 and -3 nicotinic receptor gene variants predict nicotine dependence but not cessation: findings from the COMMIT cohort.
Alpha-5 and -3 nicotinic receptor gene variants predict nicotine dependence but not cessation: findings from the COMMIT cohort.
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DOI：
10.1002/ajmg.b.32019
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发表时间：
2012-03
影响因子：
2.8
通讯作者：
Hyland, Andrew
中科院分区：
文献类型：
--
作者：
Bousman, Chad A.;Rivard, Cheryl;Den Haese, Jason;Ambrosone, Christine;Hyland, Andrew
每天吸烟多（CPD）和醒来后第一支烟间隔时间短（TTF）是两种最具遗传性的吸烟表型，并构成重度吸烟指数（HSI）。这些表型通常被用作尼古丁依赖（ND）的代理，并与戒烟结果相关。病例对照和全基因组关联研究报道了α -5和-3尼古丁受体亚基（CHRNA5和CHRNA3）基因的单核苷酸多态性（snp）与CPD之间的联系，但很少有研究检测TTF或戒烟结果。在这项研究中，我们在1988年至2005年的四个时间点对1301名欧洲裔美国吸烟者进行了纵向评估。一个CHRNA5 （rs16969968）和两个CHRNA3 (rs1051703, rs6495308) snp检测其预测吸烟者“曾经”报告ND的能力，基于三种表型分类：1)25+ CPD, 2) TTF < 10分钟，和3)HSI≥4。在1157名戒烟尝试者的子样本中，我们还检查了每个SNP预测“曾经”戒烟的能力，持续时间为60个月。人口统计学调整后的逻辑回归显示，所有三个snp与CPD之间存在显著的等位基因和基因型关联，但与TTF、HSI或戒烟无关。携带rs16969968-AA和rs6495308-TT基因型的人患用CPD或TTF诊断的ND的几率大约高出两倍。结果表明，根据CPD，尼古丁受体变异与ND的几率较大，与TTF的程度较小。除CPD外，研究烟碱受体遗传变异对ND表型的影响是必要的。
Smoking many cigarettes per day (CPD) and short interval to first cigarette (TTF) after waking are two of the most heritable smoking phenotypes and comprise the Heavy Smoking Index (HSI). These phenotypes are often used as proxies for nicotine dependence (ND) and are associated with smoking cessation outcomes. Case-control and genome-wide association studies have reported links between single nucleotide polymorphisms (SNPs) in the alpha-5 and -3 nicotinic receptor subunit (CHRNA5 and CHRNA3) genes and CPD but few have examined TTF or cessation outcomes. In this study we longitudinally assessed 1301 European-American smokers at four time-points from 1988 to 2005. One CHRNA5 (rs16969968) and two CHRNA3 (rs1051703, rs6495308) SNPs were examined for their ability to predict smokers who ‘ever’ reported ND based on three phenotypic classifications: 1) 25+ CPD, 2) TTF < 10 minutes, and 3) HSI ≥ 4. In a subsample of 1157 quit attempters, we also examined each SNP’s ability to predict ‘ever’ quitting for a period of >6 months. Demographically adjusted logistic regressions showed significant allelic and genotypic associations between all three SNPs and CPD but not TTF, HSI, or smoking cessation. Carriers of both the rs16969968-AA and rs6495308-TT genotypes had approximately two-fold greater odds for ND defined using CPD or TTF. Results suggest nicotinic receptor variants are associated with greater odds of ND according to CPD and to a lesser extent TTF. Research examining the effect of nicotinic receptor genetic variation on ND phenotypes beyond CPD is warranted.
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DOI：
10.1002/ajmg.b.30828
发表时间：
2009-06-05
期刊：
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
影响因子：
--
作者：
Saccone NL;Saccone SF;Hinrichs AL;Stitzel JA;Duan W;Pergadia ML;Agrawal A;Breslau N;Grucza RA;Hatsukami D;Johnson EO;Madden PA;Swan GE;Wang JC;Goate AM;Rice JP;Bierut LJ
通讯作者：
Bierut LJ
影响因子：
3.7
作者：
Caporaso N;Gu F;Chatterjee N;Sheng-Chih J;Yu K;Yeager M;Chen C;Jacobs K;Wheeler W;Landi MT;Ziegler RG;Hunter DJ;Chanock S;Hankinson S;Kraft P;Bergen AW
通讯作者：
Bergen AW
影响因子：
6.9
作者：
Lessov, CN;Martin, NG;Madden, PAF
通讯作者：
Madden, PAF
影响因子：
4.4
作者：
Chabrol, H;Niezborala, M;de Leon, J
通讯作者：
de Leon, J
影响因子：
11.2
作者：
Saccone NL;Wang JC;Breslau N;Johnson EO;Hatsukami D;Saccone SF;Grucza RA;Sun L;Duan W;Budde J;Culverhouse RC;Fox L;Hinrichs AL;Steinbach JH;Wu M;Rice JP;Goate AM;Bierut LJ
通讯作者：
Bierut LJ