Significant associations of CHRNA2 and CHRNA6 with nicotine dependence in European American and African American populations.
Significant associations of CHRNA2 and CHRNA6 with nicotine dependence in European American and African American populations.
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DOI：
10.1007/s00439-013-1398-9
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发表时间：
2014-05
期刊：
影响因子：
5.3
通讯作者：
Li, Ming D.
中科院分区：
文献类型：
--
作者：
Wang, Shaolin;van der Vaart, Andrew D.;Xu, Qing;Seneviratne, Chamindi;Pomerleau, Ovide F.;Pomerleau, Cynthia S.;Payne, Thomas J.;Ma, Jennie Z.;Li, Ming D.
尼古丁依赖(ND)的直接生理效应是由烟碱型乙酰胆碱受体(NAChRs)介导的。根据成瘾的遗传和药理学基础，许多先前的研究发现，在不同种族样本中，nAChR亚单位基因变异与ND的各种测量方法之间存在显著关联。在这项研究中，我们首先使用一个由来自495个家庭的1,730名欧洲裔美国人(EA)和来自424个家庭的1,892名非洲裔美国人(定义为发现家族样本)组成的家庭样本，研究了8号染色体上nAChR亚单位α2和α6基因变异与ND的关联。通过吸烟量(SQ)和新城疫Fagerström试验(FTND)两种标准定量测量方法对新城疫进行评估。我们发现所有七个被测试基因的SNPs与EA样本中的至少一个ND测量和AA样本中CHRNA2中的两个SNPs名义上存在关联。其中，rs3735757与FTND(P=0.0068)和rs2472553与两种ND指标(SQ和FTND的P值分别为0.0043和0.00086)的相关性在EA样本中仍然显著，即使在对多个测试进行校正后也是如此。此外，我们在CHRNA6的EA样本以及CHRNA2的EA和AA样本中发现了几个与ND显著相关的单倍型。为了确认这两个基因与ND的相关性，我们对SAGE研究中的一个独立病例对照样本进行了重复研究，结果表明这两个基因与ND有显著的相关性，尽管在两个样本中显著相关的SNP并不总是相同的。综上所述，这些发现表明CHRNA2和CHRNA6在AA和EA吸烟者ND的病因学中起重要作用。在更多的独立样品中进一步复制是有保证的。
The direct physiological effects that promote nicotine dependence (ND) are mediated by nicotinic acetylcholine receptors (nAChRs). In line with the genetic and pharmacological basis of addiction, many previous studies have revealed significant associations between variants in the nAChR subunit genes and various measures of ND in different ethnic samples. In this study, we first examined the association of variants in nAChR subunits α2 (CHRNA2) and α6 (CHRNA6) genes on chromosome 8 with ND using a family sample consisting of 1,730 European Americans (EAs) from 495 families and 1,892 African Americans (AAs) from 424 families (defined as the discovery family sample). ND was assessed by two standard quantitative measures: Smoking Quantity (SQ) and the Fagerström Test for ND (FTND). We found nominal associations for all seven tested SNPs of the genes with at least one ND measure in the EA sample and for two SNPs in CHRNA2 in the AA sample. Of these, associations of SNPs rs3735757 with FTND (P = 0.0068) and rs2472553 with both ND measures (with a P value of 0.0043 and 0.00086 for SQ and FTND, respectively) continued to be significant in the EA sample even after correction for multiple tests. Further, we found several haplotypes that were significantly associated with ND in the EA sample in CHRNA6 and in the both EA and AA samples in CHRNA2. To confirm the associations of the two genes with ND, we conducted a replication study with an independent case-control sample from the SAGE study, which showed a significant association of the two genes with ND, although the significantly associated SNPs were not always the same in the two samples. Together, these findings indicate that both CHRNA2 and CHRNA6 play a significant role in the etiology of ND in AA and EA smokers. Further replication in additional independent samples is warranted.
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DOI：
10.1111/j.1601-183x.2009.00495.x
发表时间：
2009-08
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Hoft NR;Corley RP;McQueen MB;Huizinga D;Menard S;Ehringer MA
通讯作者：
Ehringer MA
影响因子：
5.3
作者：
Gotti, Cecilia;Guiducci, Stefania;Zoli, Michele
通讯作者：
Zoli, Michele
DOI：
10.1038/npp.2008.122
发表时间：
2009-02
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
4.4
作者：
FAGERSTROM, KO
通讯作者：
FAGERSTROM, KO