Sander T, Harms H, Podschus J, Finckh U, Nickel B, Rolfs A, Rommelspacher H, Schmidt L G
Department of Psychiatry, Free University of Berlin, Germany.
Psychiatr Genet. 1995 Winter;5(4):171-6. doi: 10.1097/00041444-199524000-00004.
Hereditary factors play a substantial role in the etiology of alcohol dependence. Alcohol mediates its reinforcing effects by an activation of the mesolimbic dopamine system. These findings suggest that the genes encoding the dopamine receptor (DR) subtypes represent high-ranking candidates for susceptibility genes to addictive disorders. Our present population-based association study investigated whether sequence variants of the dopamine D1, D2 and D3 receptor genes confer susceptibility to alcohol dependence in 278 alcoholics, and clinically more homogeneous subgroups ascertained through positive family history, early age at onset, delirium, withdrawal seizures and antisocial tendencies. No evidence for an allelic association was found for the PCR-based TaqA RFLP fo the DRD2 gene and a Bsp1286I RFLP of the DRD1 gene. Without correction for multiple testing, we found a significantly increased allele frequency of a common DRD3 gene variant expressing a serine at position 9 in the extracellular N-terminal part of the receptor protein in 55 alcohol-dependent individuals with delirium (chi 2 = 4.1, df = 1, p = 0.042). Further studies have to examine whether this amino acid substitution or a nearby mutation confers genetic susceptibility to at least a subgroup of alcohol-dependent individuals with delirium.
遗传因素在酒精依赖的病因学中起着重要作用。酒精通过激活中脑边缘多巴胺系统来介导其强化作用。这些发现表明，编码多巴胺受体（DR）亚型的基因是成瘾性障碍易感基因的重要候选者。我们目前基于人群的关联研究调查了多巴胺D1、D2和D3受体基因的序列变异是否会使278名酗酒者以及通过阳性家族史、早发、谵妄、戒断性癫痫发作和反社会倾向确定的临床更同质的亚组易患酒精依赖。对于基于PCR的DRD2基因TaqA RFLP和DRD1基因Bsp1286I RFLP，未发现等位基因关联的证据。在未进行多重检验校正的情况下，我们发现55名伴有谵妄的酒精依赖个体中，一种常见的DRD3基因变体的等位基因频率显著增加，该变体在受体蛋白细胞外N末端第9位表达丝氨酸（χ2 = 4.1，自由度 = 1，p = 0.042）。进一步的研究必须检验这种氨基酸替代或附近的突变是否赋予至少一部分伴有谵妄的酒精依赖个体遗传易感性。
