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与酒精中毒相关的表型及CB1受体的基因变异

Alcoholism-related phenotypes and genetic variants of the CB1 receptor.

作者信息

Preuss U W, Koller G, Zill P, Bondy B, Soyka M

机构信息

Psychiatrische Klinik und Poliklinik, Ludwig-Maximilians-Universität Muenchen, Nussbaumstr. 7, 80336 München, Germany.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2003 Dec;253(6):275-80. doi: 10.1007/s00406-003-0440-7.

DOI:10.1007/s00406-003-0440-7
PMID:14714115
Abstract

OBJECTIVE

Neurotransmitter release of GABAergic and glutamatergic neurons may be significantly influenced by cannabinoid CB1 receptors located at presynaptic nerve terminals. GABA and glutamate have been reported to be involved in the pathogenesis of severe alcohol withdrawal-induced seizures and delirium tremens. The aim of this study is to test the potential influence of a bi-allelic cannabinoid receptor gene (CNR1) polymorphism (G1359A) on severe alcohol withdrawal syndromes.

METHODS

Based upon a sample size estimation, 196 subjects meeting DSM IV and ICD10 criteria for alcohol dependence and 210 non-alcoholic controls were recruited for study. CB1 polymorphisms were determined using polymerase chain reaction (PCR). History of alcohol withdrawal-induced delirium tremens, seizures and other alcohol withdrawal-related phenotypes were obtained using the SSAGA (Semi-Structured Assessment of Genetics in Alcoholism). Data were corroborated with information from the inpatients' clinical files.

RESULTS

Allele frequencies of the CNR1 G1359A polymorphism were within the range reported by previous studies. After correcting for multiple testing, no association of the A- or G-allele of CNR1 polymorphism with a history of alcohol withdrawal-induced seizures was detected. In addition, no significant relationships with other alcoholism-related phenotypes were found.

CONCLUSION

This study failed to confirm an earlier report of a potential role of a CNR1 polymorphism in the pathogenesis of delirium tremens.

摘要

目的

位于突触前神经末梢的大麻素CB1受体可能会显著影响γ-氨基丁酸能和谷氨酸能神经元的神经递质释放。据报道,γ-氨基丁酸(GABA)和谷氨酸参与了严重酒精戒断所致癫痫发作和震颤谵妄的发病机制。本研究旨在测试双等位基因大麻素受体基因(CNR1)多态性(G1359A)对严重酒精戒断综合征的潜在影响。

方法

根据样本量估计,招募了196名符合DSM-IV和ICD-10酒精依赖标准的受试者以及210名非酒精依赖对照者进行研究。使用聚合酶链反应(PCR)确定CB1基因多态性。通过酒精中毒遗传学半结构化评估(SSAGA)获取酒精戒断所致震颤谵妄、癫痫发作及其他与酒精戒断相关表型的病史。数据与住院患者临床档案中的信息进行了核对。

结果

CNR1 G1359A多态性的等位基因频率在先前研究报道的范围内。在进行多重检验校正后,未检测到CNR1多态性的A等位基因或G等位基因与酒精戒断所致癫痫发作病史之间存在关联。此外,未发现与其他酒精中毒相关表型有显著关系。

结论

本研究未能证实先前关于CNR1多态性在震颤谵妄发病机制中潜在作用的报道。

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