Association of the DRD4 Exon III polymorphism with smoking in fifteen-year-olds: A mediating role for novelty seeking?
Association of the DRD4 Exon III polymorphism with smoking in fifteen-year-olds: A mediating role for novelty seeking?
复制标题
DOI：
10.1097/01.chi.0000155980.01792.7f
复制
发表时间：
2005-05-01
影响因子：
13.3
通讯作者：
Schmidt, MH
中科院分区：
文献类型：
--
作者：
Laucht, M;Becker, K;Schmidt, MH
目的：本研究旨在检查多巴胺 D4 受体基因 (DRD4) 的 DNA 变异在青少年吸烟实验中的作用，并确定新颖性寻求 (NS) 在多大程度上可以解释 DRD4 对烟草使用的可能影响。方法：参与者来自对原始出生队列（1986-1988 年出生）的纵向研究，其中包括来自高危社区样本的 384 名儿童。 15 岁时，青少年完成了一份测量烟草消费和气质的自我报告问卷（青少年气质和性格调查表）。从 303 名参与者（144 名男性，159 名女性）中提取 DNA 并进行 DRD4 外显子 III 多态性基因分型。结果：DRD4 与男性吸烟状况和 NS 相关，但与女性无关。与没有该等位基因的男性相比，具有七个重复等位基因的男性表现出更多的吸烟参与度 (p < .002)，并且 NS 得分更高 (p < .002)。此外，男性和女性吸烟率升高与 NS 水平升高相关 (p < .001)。多元回归分析表明，NS 介导了男性 DRD4 与吸烟之间的关系。结论：这些发现强调了按性别以及可能按发育时期分别考虑遗传因素与烟草使用之间关联机制的重要性。
Objective: This study was designed to examine the role of DNA variants of the dopamine D4 receptor gene (DRD4) in smoking experimentation in adolescents and to determine the extent to which novelty seeking (NS) could account for a possible effect of DRD4 on tobacco use. Method: Participants were from a longitudinal study of an original birth cohort (born 1986-1988) of 384 children from a high-risk community sample. At age 15 years, adolescents completed a self-report questionnaire measuring tobacco consumption and temperament (Junior Temperament and Character Inventory). DNA was taken from 303 participants (144 males, 159 females) and genotyped for the DRD4 exon III polymorphism. Results: DRD4 was associated with smoking status and NS in males but not in females. Males with the seven repeat allele exhibited more smoking involvement (p < .002) and scored higher in NS (p < .002) than males without this allele. In addition, elevated tobacco use was related to a higher level of NS in both males and females (p < .001). Multiple regression analyses revealed that NS mediated the relationship between DRD4 and smoking in males. Conclusions: These findings highlight the importance of considering the mechanisms underlying the association between genetic factors and tobacco use separately by gender and, possibly, by developmental period.