Genetic association of the CHRNA6 and CHRNB3 genes with tobacco dependence in a nationally representative sample.
Genetic association of the CHRNA6 and CHRNB3 genes with tobacco dependence in a nationally representative sample.
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DOI：
10.1038/npp.2008.122
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发表时间：
2009-02
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影响因子：
--
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神经型烟碱型乙酰胆碱受体既可被内源性乙酰胆碱激活，也可被外源性尼古丁激活，因此这些受体的序列变异可能与烟草表型有关。以前的研究已经发现，包含CHRNA6和CHRNB3基因的基因组区域的SNPs与烟草行为之间存在显著的关联。在这项研究中，我们在国家青年调查家庭研究第10波中支持这些基因与烟草依赖之间的关联，这是一个具有全国代表性的家庭样本。在1051名受试者中，对CHRNA6和CHRNB3基因组区域的8个单核苷酸多态(SNPs)进行了基因分型，其中大约一半是同胞对成员。使用基于家庭的方法评估与DSM-IV依赖的遗传关联，如在统计程序包PBAT中实施的那样。对单个SNP与戒烟尝试和全面依赖的关联进行了测试。研究发现，CHRNA6基因的变异与烟草依赖有关(在高加索人中p=0.007)。CHRNB3中的SNP与戒烟尝试次数相关(p=0.0024)。总而言之，这些结果进一步表明CHRNA6下游区域和CHRNB3上游区域存在尼古丁依赖的风险。
Neuronal nicotinic acetylcholine receptors are activated by both endogenous acetylcholine and exogenous nicotine, making sequence variations in these receptors likely candidates for association with tobacco phenotypes. Previous studies have found evidence for significant association between SNPs in the genomic region containing the CHRNA6 and CHRNB3 genes and tobacco behaviors. In this study, we provide support for an association between these genes and tobacco dependence in the National Youth Survey Family Study wave 10, a nationally representative sample of households. Eight single nucleotide polymorphisms (SNPs) in the CHRNA6 and CHRNB3 genomic region were genotyped in 1051 subjects, approximately half of whom are members of sibling pairs. Genetic association with DSM-IV dependence was assessed using a family-based approach as implemented in the statistical package PBAT. Individual SNPs were tested for association with quit attempts and overall dependence. Variation in CHRNA6 was found to be associated with tobacco dependence (p=0.007 in Caucasians). SNPs in CHRNB3 were found to be associated with the number of quit attempts (p=0.0024). Together these results further implicate the region downstream of CHRNA6 and the region upstream of CHRNB3 in risk of nicotine dependence.
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DOI：
10.1073/pnas.89.13.5847
发表时间：
1992-07-01
影响因子：
11.1
作者：
ZHANG, L;CUI, XF;ARNHEIM, N
通讯作者：
ARNHEIM, N
影响因子：
2.6
作者：
Anchordoquy, HC;McGeary, C;Smolen, A
通讯作者：
Smolen, A
影响因子：
64.8
作者：
Gibbs, RA;Belmont, JW;Tanaka, T
通讯作者：
Tanaka, T
影响因子：
4.3
作者：
Brant-Zawadzki, Peter B.;Schmid, Douglas I.;Kraiss, Larry W.
通讯作者：
Kraiss, Larry W.
影响因子：
--
作者：
Rhee, SH;Hewitt, JK;Stallings, MC
通讯作者：
Stallings, MC