Association between CHRNA5 genetic variation at rs16969968 and brain reactivity to smoking images in nicotine dependent women.
Association between CHRNA5 genetic variation at rs16969968 and brain reactivity to smoking images in nicotine dependent women.
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DOI：
10.1016/j.drugalcdep.2011.06.009
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发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Kaufman, Marc J.
中科院分区：
文献类型：
--
作者：
Janes, Amy C.;Smoller, Jordan W.;David, Sean P.;Frederick, Blaise deB.;Haddad, Stephen;Basu, Aditi;Fava, Maurizio;Evins, A. Eden;Kaufman, Marc J.
吸烟是发达国家可预防的主要死因。确定吸烟的危险因素可能会导致更有效的治疗。全基因组关联研究揭示了尼古丁依赖的发展与尼古丁乙酰胆碱受体（nAChR）α-5亚基基因（CHRNA 5）的单核苷酸多态性（SNP，rs 16969968）之间的关系。该SNP与其他吸烟行为因素（如吸烟提示反应）之间的关系尚不清楚。我们评估rs 16969968对大脑功能磁共振成像（fMRI）反应性吸烟线索的作用，通过研究尼古丁依赖的妇女与尼古丁依赖的“风险”等位基因（A等位基因，N=14）和没有“风险”等位基因（G/G吸烟者，N=10）。尼古丁依赖的严重程度，评估与尼古丁依赖，吸烟包年，和过期的一氧化碳水平的Fagerstrom测试，在这些组中是等同的。我们观察到了fMRI反应的组间差异;没有A等位基因的女性（G/G吸烟者）在与记忆和习惯行为相关的大脑区域（如海马体和背侧纹状体）对吸烟图像表现出更大的fMRI反应。我们的发现表明，缺乏rs 16969968 A等位基因的尼古丁依赖性吸烟者比A等位基因吸烟者更容易回忆起吸烟相关的记忆，并对吸烟线索做出习惯性反应。虽然需要更多的研究来确定这种线索反应差异的机制和意义，但这些数据表明，吸烟者可能会因不同的因素（包括遗传和线索反应）而产生并保持尼古丁依赖。这一发现可能对个性化吸烟治疗有影响。
Tobacco smoking is the leading preventable cause of death in the developed world. Identifying risk factors for smoking may lead to more effective treatments. Genome wide association studies revealed a relationship between development of nicotine dependence and a single-nucleotide polymorphism (SNP, rs16969968) of the nicotine acetylcholine receptor (nAChR) alpha-5 subunit gene (CHRNA5). The relationship between this SNP and other factors contributing to smoking behavior such as smoking cue reactivity is unclear. We assessed the role of rs16969968 on brain functional MRI (fMRI) reactivity to smoking cues by studying nicotine dependent women with the nicotine dependence ‘risk’ allele (A allele, N=14) and without the ‘risk’ allele (G/G smokers, N=10). Nicotine dependence severity, as assessed with the Fagerstrom test for nicotine dependence, smoking pack-years, and expired carbon monoxide levels, were equivalent in these groups. We observed a group difference in fMRI reactivity; women without the A allele (G/G smokers) showed greater fMRI reactivity to smoking images in brain areas related to memory and habitual behavior such as the hippocampus and dorsal striatum. Our finding suggests that nicotine-dependent smokers lacking the rs16969968 A allele are more likely to recall smoking-related memories and engage in habitual responding to smoking cues than A allele smokers. Although more studies are necessary to determine the mechanism underlying and significance of this cue reactivity difference, these data suggest that smokers may develop and remain nicotine dependent due to different factors including genetics and cue reactivity. This finding may have implications for personalizing smoking treatment.
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DOI：
10.1111/j.1460-9568.2009.07058.x
发表时间：
2010-02
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Jia Y;Yamazaki Y;Nakauchi S;Ito K;Sumikawa K
通讯作者：
Sumikawa K
DOI：
10.1073/pnas.1004745107
发表时间：
2010-07-27
影响因子：
11.1
作者：
Hong, L. Elliot;Hodgkinson, Colin A.;Stein, Elliot A.
通讯作者：
Stein, Elliot A.
影响因子：
7.6
作者：
Kosten, TR;Scanley, BE;Wexler, BE
通讯作者：
Wexler, BE
影响因子：
7.6
作者：
Franklin, Teresa R.;wang, Ze;Childress, Anna Rose
通讯作者：
Childress, Anna Rose
影响因子：
3.6
作者：
Kuryatov, Alexandre;Onksen, Jennifer;Lindstrom, Jon
通讯作者：
Lindstrom, Jon