Uhl G, Blum K, Noble E, Smith S
Laboratory of Molecular Neurobiology, National Institute on Drug Abuse, Baltimore, MD 21224.
Trends Neurosci. 1993 Mar;16(3):83-8. doi: 10.1016/0166-2236(93)90128-9.
Dopamine systems are key to the actions of several substances. Inter-individual differences in genes encoding proteins involved in dopaminergic neurotransmission could plausibly explain some of the genetic bases for inter-individual differences in vulnerability to substance abuse. The restriction fragment length polymorphism (RFLP) markers TaqIA1 and B1 at the dopamine D2 receptor (DRD2) gene locus in Caucasians are associated with substance abuse behaviors. In most, but not all, studies of alcoholics and polysubstance abusers, these TaqIA1 and B1 gene markers are present more often in substance abusers than in control individuals. No study has identified substance abusers or controls by sampling randomly from the general population; allelic association findings could thus conceivably be confounded by RFLP differences based on ethnicity or other factors. However, meta-analyses of the data from controlled studies available to date are consistent with the proposal that DRD2 gene variants contribute to inter-individual differences in vulnerability to alcoholism and polysubstance abuse.
多巴胺系统是多种物质发挥作用的关键。编码参与多巴胺能神经传递的蛋白质的基因存在个体差异，这可能合理地解释了个体在药物滥用易感性方面存在个体差异的一些遗传基础。高加索人中，位于多巴胺D2受体（DRD2）基因位点的限制性片段长度多态性（RFLP）标记TaqIA1和B1与药物滥用行为有关。在大多数（但并非所有）针对酗酒者和多种物质滥用者的研究中，这些TaqIA1和B1基因标记在药物滥用者中出现的频率高于对照组个体。尚无研究通过从普通人群中随机抽样来确定药物滥用者或对照组；因此，基于种族或其他因素的RFLP差异可能会混淆等位基因关联研究的结果。然而，对现有对照研究数据的荟萃分析与以下观点一致：DRD2基因变异导致个体在酒精中毒和多种物质滥用易感性方面存在差异。
