Sander T, Harms H, Podschus J, Finckh U, Nickel B, Rolfs A, Rommelspacher H, Schmidt L G
Department of Psychiatry, University Hospital Benjamin Franklin, Free University of Berlin, Germany.
Biol Psychiatry. 1997 Feb 1;41(3):299-304. doi: 10.1016/s0006-3223(96)00044-3.
Hereditary factors confer susceptibility to alcohol dependence. Alcohol mediates its reinforcing effects by enhancing dopamine activity in the mesolimbic dopamine system. The role of the dopamine transporter in terminating dopaminergic activity in synaptic neurotransmission suggests that variants of the dopamine transporter gene (DAT1) might contribute to individual differences in vulnerability to addictive behavior. Our population-based association study investigated whether variants of DAT1 confer susceptibility to alcohol dependence in 293 alcoholics and clinically more homogeneous subgroups formed by: positive family history, early age-at-onset, delirium, withdrawal seizures, antisocial tendencies, type 1 and 2 alcoholics. Analyzing a VNTR polymorphism in the 3' untranslated region of DAT1, we found a significantly increased prevalence of the nine-repeat allele in 93 alcoholics displaying withdrawal seizures or delirium, compared with 93 ethnically matched nonalcoholic controls (p = 0.003; OR = 2.44; 95% confidence interval: 1.35-4.43). Our data provide evidence that a major genetic determinant of DAT1 influences vulnerability to severe alcohol withdrawal symptoms.
遗传因素使人易患酒精依赖症。酒精通过增强中脑边缘多巴胺系统中的多巴胺活性来介导其强化作用。多巴胺转运体在终止突触神经传递中的多巴胺能活性方面所起的作用表明，多巴胺转运体基因（DAT1）的变异可能导致个体在成瘾行为易感性上的差异。我们基于人群的关联研究调查了DAT1的变异是否会使293名酗酒者以及按以下因素形成的临床同质性更高的亚组易患酒精依赖症：阳性家族史、早发年龄、谵妄、戒断性癫痫发作、反社会倾向、1型和2型酗酒者。通过分析DAT1 3'非翻译区的一个可变数目串联重复多态性，我们发现，与93名种族匹配的非酗酒对照者相比，93名出现戒断性癫痫发作或谵妄的酗酒者中九重复等位基因的患病率显著增加（p = 0.003；比值比 = 2.44；95%置信区间：1.35 - 4.43）。我们的数据提供了证据，表明DAT1的一个主要遗传决定因素会影响对严重酒精戒断症状的易感性。
