Rossing M A
Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA.
Environ Health Perspect. 1998 May;106(5):231-8. doi: 10.1289/ehp.98106231.
Twin studies consistently indicate important genetic influences on multiple aspects of smoking behavior, including both initiation and cessation; however, knowledge regarding the role of specific genes is extremely limited. Habit-forming actions of nicotine appear to be triggered primarily at nicotinic receptors on the cell bodies of dopaminergic neurons in the mesolimbic "reward" system of the brain, a region implicated in addiction to other substances including cocaine, opiates, and alcohol. Important aspects of the dopaminergic pathway include synthesis of dopamine in dopaminergic neurons, release of dopamine by presynaptic neurons, receptor activation of postsynaptic neurons, dopamine re-uptake by presynaptic neurons, and metabolism of released dopamine. Research examining the role of allelic variation in genes involved in these functions is being actively pursued with respect to addictive behavior as well as personality traits and psycho- and neuropathologic conditions and has implications for smoking research. In addition, genetic differences in nicotinic receptors or nicotine metabolism might reasonably be hypothesized to play a role in smoking addiction. A role of dopaminergic or other genes in smoking cessation is of particular potential importance, as research in this area may lead to the identification of subgroups of individuals for whom pharmacologic cessation aids may be most effective.
双胞胎研究一直表明，基因对吸烟行为的多个方面有着重要影响，包括开始吸烟和戒烟；然而，关于特定基因作用的知识极为有限。尼古丁的成瘾行为似乎主要在大脑中脑边缘“奖赏”系统多巴胺能神经元细胞体上的烟碱型受体处触发，该区域与对包括可卡因、阿片类药物和酒精在内的其他物质成瘾有关。多巴胺能通路的重要方面包括多巴胺能神经元中多巴胺的合成、突触前神经元释放多巴胺、突触后神经元的受体激活、突触前神经元对多巴胺的再摄取以及释放的多巴胺的代谢。关于这些功能相关基因中等位基因变异作用的研究，正针对成瘾行为、人格特质以及心理和神经病理状况积极展开，这对吸烟研究也有启示意义。此外，可以合理推测烟碱型受体或尼古丁代谢方面的基因差异在吸烟成瘾中起作用。多巴胺能或其他基因在戒烟中的作用尤其具有潜在重要性，因为该领域的研究可能会确定哪些亚组个体使用药物戒烟辅助手段最为有效。
