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酒精使用障碍的精神分裂症患者中GABRG2基因多态性与自杀行为的关联研究。

Association study of GABRG2 polymorphisms with suicidal behaviour in schizophrenia patients with alcohol use disorder.

作者信息

Zai Clement C, Zai Gwyneth C, Tiwari Arun K, Manchia Mirko, de Luca Vincenzo, Shaikh Sajid A, Strauss John, Kennedy James L

机构信息

Neurogenetics Section, Neuroscience Research Department, Centre for Addiction and Mental Health, Toronto, Ont., Canada.

出版信息

Neuropsychobiology. 2014;69(3):154-8. doi: 10.1159/000358839. Epub 2014 Apr 26.

Abstract

BACKGROUND

Schizophrenia is a severe neuropsychiatric disorder where the role of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter, has been implicated in its aetiopathophysiology. Several genes coding for GABAA subunits, including the GABRG2 gene that encodes the γ2 subunit, are clustered at 5q31-q35, a chromosomal region that is associated with schizophrenia in genome scan studies. We recently reported GABRG2 to be associated with schizophrenia in our case-control and family samples.

METHODS

We tested eight single-nucleotide polymorphisms spanning the GABRG2 gene for an association with suicidal behaviour in our schizophrenia sample of European ancestry (n = 197), taking into account history of alcohol abuse or dependence.

RESULTS

We found the haplotypes of the rs183294 and rs209356 markers to be significantly associated with history of suicide attempt (p < 0.01) as well as suicide specifier scores (p < 0.05). The association appeared to be originating in patients with a history of alcohol dependence or abuse.

CONCLUSIONS

Taken together, the results of the present study suggest that GABRG2 may be involved in suicidal behaviour in schizophrenia patients with alcohol dependence or abuse, but replications are required. These results may help in the discovery of novel treatments for alcoholism and/or prevention of suicide.

摘要

背景

精神分裂症是一种严重的神经精神障碍,其中抑制性神经递质γ-氨基丁酸(GABA)在其病因病理生理学中发挥作用。几个编码GABAA亚基的基因,包括编码γ2亚基的GABRG2基因,聚集在5q31 - q35,这是一个在基因组扫描研究中与精神分裂症相关的染色体区域。我们最近在病例对照和家系样本中报道GABRG2与精神分裂症相关。

方法

我们在欧洲血统的精神分裂症样本(n = 197)中,检测了跨越GABRG2基因的8个单核苷酸多态性与自杀行为的关联,并考虑了酒精滥用或依赖史。

结果

我们发现rs183294和rs209356标记的单倍型与自杀未遂史(p < 0.01)以及自杀特征评分(p < 0.05)显著相关。这种关联似乎源于有酒精依赖或滥用史的患者。

结论

综上所述,本研究结果表明GABRG2可能参与有酒精依赖或滥用的精神分裂症患者的自杀行为,但需要重复验证。这些结果可能有助于发现酒精中毒的新疗法和/或预防自杀。

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