Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland, Australia.
Drug Alcohol Depend. 2011 Apr 1;114(2-3):140-6. doi: 10.1016/j.drugalcdep.2010.08.014. Epub 2010 Oct 28.
The C allele of a common polymorphism of the serotonin 2A receptor (HTR2A) gene, T102C, results in reduced synthesis of 5-HT2A receptors and has been associated with current smoking status in adults. The -1438A/G polymorphism, located in the regulatory region of this gene, is in linkage disequilibrium with T102C, and the A allele is associated with increased promoter activity and with smoking in adult males. We investigated the contributions of the HTR2A gene, chronic psychological stress, and impulsivity to the prediction of cigarette smoking status and dependence in young adults.
T102C and -1438A/G genotyping was conducted on 132 healthy Caucasian young adults (47 smokers) who completed self-report measures of chronic stress, depressive symptoms, impulsive personality and cigarette use.
A logistic regression analysis of current cigarette smoker user status, after adjusting for gender, depressive symptom severity and chronic stress, indicated that the T102C TT genotype relative to the CC genotype (OR=7.53), and lower punishment sensitivity (OR=0.91) were each significant predictive risk factors. However, for number of cigarettes smoked, only lower punishment sensitivity was a significant predictor (OR=0.81).
These data indicate the importance of the T102C polymorphism to tobacco use but not number of cigarettes smoked for Caucasian young adults. Future studies should examine whether this is explained by effects of nicotine on the serotonin system. Lower punishment sensitivity increased risk of both smoking and of greater consumption, perhaps via a reduced sensitivity to cigarette health warnings and negative physiological effects.
5-羟色胺 2A 受体(HTR2A)基因的常见多态性的 C 等位基因 T102C 导致 5-HT2A 受体合成减少,并且与成年人的当前吸烟状态有关。位于该基因调控区域的-1438A / G 多态性与 T102C 连锁不平衡,A 等位基因与启动子活性增加以及成年男性吸烟有关。我们研究了 HTR2A 基因、慢性心理压力和冲动性对预测年轻成年人吸烟状况和依赖的贡献。
对 132 名健康的白种年轻成年人(47 名吸烟者)进行了 T102C 和-1438A / G 基因分型,他们完成了慢性压力、抑郁症状、冲动人格和吸烟的自我报告测量。
在调整性别、抑郁症状严重程度和慢性压力后,对当前吸烟者使用状态的逻辑回归分析表明,T102C TT 基因型相对于 CC 基因型(OR=7.53),以及较低的惩罚敏感性(OR=0.91)都是显著的预测风险因素。然而,对于吸烟量,只有较低的惩罚敏感性是一个显著的预测因子(OR=0.81)。
这些数据表明 T102C 多态性对吸烟但不是吸烟量对高加索年轻成年人的重要性。未来的研究应该检查这是否可以通过尼古丁对 5-羟色胺系统的影响来解释。较低的惩罚敏感性增加了吸烟和消费增加的风险,可能是通过降低对吸烟健康警告和负面生理效应的敏感性。