Brain Imaging Center, McLean Hospital, Harvard Medical School, 115 Mill St., Belmont, MA 02478, USA.
Drug Alcohol Depend. 2012 Jan 1;120(1-3):7-13. doi: 10.1016/j.drugalcdep.2011.06.009. Epub 2011 Jul 20.
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.
吸烟是发达国家中可预防的主要死亡原因。确定吸烟的风险因素可能会导致更有效的治疗方法。全基因组关联研究显示，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（CHRNA5）的单核苷酸多态性（SNP，rs16969968）之间存在关系。该 SNP 与其他导致吸烟行为的因素（如吸烟线索反应性）之间的关系尚不清楚。
我们通过研究具有尼古丁依赖“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）的尼古丁依赖女性，评估了 rs16969968 对吸烟线索的脑功能磁共振成像（fMRI）反应的作用。这些组在尼古丁依赖严重程度（用尼古丁依赖 Fagerstrom 测试评估）、吸烟包年数和呼出的一氧化碳水平方面相当。
我们观察到 fMRI 反应存在组间差异；没有 A 等位基因（G/G 吸烟者）的女性在与记忆和习惯性行为相关的大脑区域（如海马体和背侧纹状体）对吸烟图像的 fMRI 反应更大。
我们的发现表明，缺乏 rs16969968 A 等位基因的尼古丁依赖吸烟者比 A 等位基因吸烟者更有可能回忆起与吸烟相关的记忆，并对吸烟线索产生习惯性反应。尽管还需要更多的研究来确定这种线索反应差异的潜在机制和意义，但这些数据表明，由于包括遗传学和线索反应性在内的不同因素，吸烟者可能会发展并保持尼古丁依赖。这一发现可能对个性化吸烟治疗具有重要意义。
