Interaction between the dopamine D4 receptor and the serotonin transporter promoter polymorphisms in alcohol and tobacco use among 15-year-olds
Interaction between the dopamine D4 receptor and the serotonin transporter promoter polymorphisms in alcohol and tobacco use among 15-year-olds
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DOI：
10.1007/s10048-006-0050-4
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发表时间：
2006-11-01
期刊：
影响因子：
2.2
通讯作者：
Schmidt, M. H.
中科院分区：
文献类型：
--
作者：
Skowronek, M. H.;Laucht, M.;Schmidt, M. H.
青少年时期过早开始使用酒精和烟草会增加成年后出现物质使用障碍的风险。酒精和尼古丁都会刺激多巴胺（DA）和血清素（5-HT）系统。DA系统被认为与自我给药滥用的奖励效应的中介有关。这些神经递质系统之间的相互作用可能在物质使用行为中起作用，但目前尚不清楚。本研究旨在探讨DA D4受体（DRD4）和5-羟色胺转运体（5-HTT）基因型对青少年酒精和烟草实验的影响及其相互作用。参与者来自一项出生队列的纵向研究，该队列最初由来自高危社区样本的384名儿童组成。在15岁时，青少年完成一份测量烟草和酒精消费的自我报告问卷。从305名参与者（146名男孩，159名女孩）中提取DNA，并对DRD4外显子III和5-HTTLPR多态性进行基因分型。drd47重复等位基因与男孩更多的吸烟和饮酒有关。在女孩中，检测到显著的DRD4 x 5-HTT相互作用。无DRD4 7重复等位基因和5-HTTLPR长等位基因纯合的女孩吸烟和饮酒活性最高。遗传和潜在的分子背景的青少年易受药物滥用的讨论。
Early onset of alcohol and tobacco use during adolescence increases the risk for establishing a substance use disorder in adulthood. Both alcohol and nicotine stimulate the dopamine (DA) and the serotonin (5-HT) systems. The DA system has been implicated in the mediation of the rewarding effects of self-administered drugs of abuse. A possible role of an interaction between these neurotransmitter systems in substance use behavior has been suggested but is as yet unknown. The present study was designed to examine the influence of the DA D4 receptor (DRD4) and the serotonin transporter (5-HTT) genotype and their interaction on adolescent alcohol and tobacco experimentation. Participants were from a longitudinal study of a birth cohort consisting initially of 384 children from a high-risk community sample. At the age of 15 years, adolescents completed a self-report questionnaire measuring tobacco and alcohol consumption. DNA was taken from 305 participants (146 boys, 159 girls) and genotyped for the DRD4 exon III and the 5-HTTLPR polymorphisms. The DRD4 7-repeat allele was associated with greater smoking and drinking involvement in boys. In girls, a significant DRD4 x 5-HTT interaction was detected. Girls without the DRD4 7-repeat allele and who were homozygous for the long allele of 5-HTTLPR displayed the highest smoking and drinking activity. The genetic and potential molecular background underlying adolescent vulnerability to substance abuse is discussed.