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多巴胺D1和D2(TaqIA)受体基因多态性与酒精中毒多巴胺能敏感性降低缺乏等位基因关联。

Lack of allelic association of dopamine D1 and D2 (TaqIA) receptor gene polymorphisms with reduced dopaminergic sensitivity to alcoholism.

作者信息

Heinz A, Sander T, Harms H, Finckh U, Kuhn S, Dufeu P, Dettling M, Gräf K, Rolfs A, Rommelspacher H, Schmidt L G

机构信息

Psychiatric Clinic and Policlinic, Free University of Berlin, Germany.

出版信息

Alcohol Clin Exp Res. 1996 Sep;20(6):1109-13. doi: 10.1111/j.1530-0277.1996.tb01954.x.

Abstract

Our study tested the hypothesis of whether the sensitivity of central dopamine receptors corresponds to the genotypic constitution of DNA-polymorphisms of the dopamine D1 and D2 receptor (DRD1, DRD2) genes and is associated with poor treatment outcome. Therefore, 97 alcohol-dependent patients were assessed according to their sensitivity of central dopamine receptors (apomorphine-induced secretion of growth hormone), clinical outcome during a 6-month observation period, and genotypic constitution of the TaqIA restriction fragment length polymorphism (RFLP) at the DRD2 locus and of the Bsp1286I RFLP at the DRD1 locus. On the 1st day of detoxification, dopamine receptor hyposensitivity was found in treatment nonresponders, but not in responders. Apomorphine-induced growth hormone release did not differ significantly in alcoholics with different genotypes of the DRD1 and DRD2 RFLPs. Neither did we find a significant allelic association with treatment response. Thus, we did not find evidence for a genetic determination of dopamine receptor hyposensitivity in alcoholics with poor treatment outcome.

摘要

我们的研究检验了以下假设

中枢多巴胺受体的敏感性是否与多巴胺D1和D2受体(DRD1、DRD2)基因的DNA多态性的基因型构成相对应,以及是否与治疗效果不佳相关。因此,根据97例酒精依赖患者中枢多巴胺受体的敏感性(阿扑吗啡诱导的生长激素分泌)、6个月观察期内的临床结果以及DRD2基因座处的TaqIA限制性片段长度多态性(RFLP)和DRD1基因座处的Bsp1286I RFLP的基因型构成进行评估。在解毒的第一天,治疗无反应者中发现多巴胺受体低敏,而反应者中未发现。阿扑吗啡诱导的生长激素释放在DRD1和DRD2 RFLP不同基因型的酗酒者中无显著差异。我们也未发现与治疗反应有显著的等位基因关联。因此,我们没有找到证据表明治疗效果不佳的酗酒者中多巴胺受体低敏是由基因决定的。

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