Lerman C, Caporaso N E, Audrain J, Main D, Boyd N R, Shields P G
Lombardi Cancer Center (LCC), Georgetown University Medical Center, Washington, DC 20007, USA.
Mol Psychiatry. 2000 Mar;5(2):189-92. doi: 10.1038/sj.mp.4000672.
Individual differences in propensity to nicotine dependence appear to be mediated, in part, by genetic factors.1 The serotonin transporter gene has a functional polymorphism (5-HTTLPR) which modulates gene transcription and reuptake.2,3 A possible role in nicotine dependence is suggested by a link between 5-HTTLPR and neuroticism,4 a personality trait which has been related to smoking practices.5 In a cross-sectional study of 185 smokers, we utilized multiple linear regression modeling to examine the interacting effects of the 5-HTTLPR and neuroticism on smoking practices and nicotine dependence. Genotype was classified according to the presence or absence of the short (s) allele vs the long (l) allele of 5-HTTLPR (ie, s/s or s/l vs l/l). Models controlled for gender, age, race, and alcohol use. The 5-HTTLPR by neuroticism interaction effect was statistically significant in the models of nicotine intake (P = 0.05), nicotine dependence (P = 0.001), and smoking motivations (smoking to reduce negative mood (P = 0.01); smoking for stimulation (P = 0.01)). The results suggested that neuroticism was positively associated with these smoking practices among smokers with 5-HTTLPR S genotypes (s/s or s/l), but not among smokers with the L genotype (l/l). The 5-HTTLPR may modify the effects of neuroticism on smoking motivations and nicotine dependence. Assessment of 5-HTTLPR genotype and neuroticism may help to identify smokers who are more responsive to psychotropic medications, such as selective serotonin reuptake inhibitors (SSRIs), which are being used in smoking cessation treatment.
尼古丁依赖倾向的个体差异似乎部分由遗传因素介导。1 血清素转运体基因存在一种功能性多态性（5-羟色胺转运体基因连锁多态性区域，5-HTTLPR），它可调节基因转录和再摄取。2,3 5-HTTLPR 与神经质之间的联系提示其在尼古丁依赖中可能发挥作用，4 神经质是一种与吸烟行为相关的人格特质。5 在一项对 185 名吸烟者的横断面研究中，我们利用多元线性回归模型来检验 5-HTTLPR 和神经质对吸烟行为及尼古丁依赖的交互作用。根据 5-HTTLPR 的短（s）等位基因与长（l）等位基因的有无对基因型进行分类（即，s/s 或 s/l 与 l/l）。模型对性别、年龄、种族和饮酒情况进行了控制。在尼古丁摄入量模型（P = 0.05）、尼古丁依赖模型（P = 0.001）和吸烟动机模型（为减轻负面情绪而吸烟（P = 0.01）；为寻求刺激而吸烟（P = 0.01））中，5-HTTLPR 与神经质的交互作用具有统计学意义。结果表明，在具有 5-HTTLPR S 基因型（s/s 或 s/l）的吸烟者中，神经质与这些吸烟行为呈正相关，但在具有 L 基因型（l/l）的吸烟者中并非如此。5-HTTLPR 可能会改变神经质对吸烟动机和尼古丁依赖的影响。评估 5-HTTLPR 基因型和神经质可能有助于识别对精神药物（如用于戒烟治疗的选择性 5-羟色胺再摄取抑制剂，SSRIs）反应更强的吸烟者。
