Malaiyandi Viba, Sellers Edward M, Tyndale Rachel F
Department of Pharmacology and Medicine, 1 King's College Circle, University of Toronto, Canada M5S 1A8.
Clin Pharmacol Ther. 2005 Mar;77(3):145-58. doi: 10.1016/j.clpt.2004.10.011.
Nicotine is the primary addictive compound in tobacco smoke. In this review we summarize nicotine dependence and the genetics of smoking in brief before focusing on cytochrome P450 (CYP) 2A6. In humans nicotine is mainly inactivated to cotinine and CYP2A6 mediates approximately 90% of this conversion. Some, but not all, studies suggest that genetic variation in CYP2A6 may play a role in smoking. We review some of the recent findings on the influence of CYP2A6 genetic polymorphisms on nicotine kinetics, smoking behaviors, and how the gene appears to exert differential effects during various stages of smoking (eg, initiation, conversion to dependence, amount smoked during dependence, and quitting). These new findings will be put in the context of the discrepancies found in the literature. Implications of these recent findings on current and novel treatment approaches for smoking cessation and tobacco-related lung cancer will also be discussed.
尼古丁是烟草烟雾中的主要成瘾性化合物。在本综述中，我们先简要总结尼古丁依赖和吸烟的遗传学，然后重点关注细胞色素P450（CYP）2A6。在人类中，尼古丁主要被代谢为可替宁，而CYP2A6介导了约90%的这种转化。一些（但并非全部）研究表明，CYP2A6的基因变异可能在吸烟中起作用。我们回顾了一些关于CYP2A6基因多态性对尼古丁动力学、吸烟行为影响的最新研究结果，以及该基因在吸烟的各个阶段（如开始吸烟、转变为依赖、依赖期间的吸烟量和戒烟）如何表现出不同作用。这些新发现将结合文献中发现的差异进行阐述。还将讨论这些最新发现对当前及新型戒烟治疗方法和烟草相关肺癌的影响。
