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斯洛文尼亚自杀受害者的自杀、应激与血清素受体1A启动子多态性-1019C>G

Suicide, stress and serotonin receptor 1A promoter polymorphism -1019C>G in Slovenian suicide victims.

作者信息

Videtic Alja, Zupanc Tomaz, Pregelj Peter, Balazic Joze, Tomori Martina, Komel Radovan

机构信息

Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2009 Jun;259(4):234-8. doi: 10.1007/s00406-008-0861-4. Epub 2009 Feb 17.

Abstract

Implication of serotonergic system in suicide and suicide attempts has been discussed for several years. One of the most abundant serotonin receptors in the mammalian brain is the receptor 1A (5-HT1A); studies of its polymorphisms and suicide have provided very inconsistent results so far. The suggestion that the G allele depresses HTR1A autoreceptor expression, and therefore reduces serotonergic neurotransmission that might predispose to depression and suicide, made the promoter polymorphism -1019C>G a very promising candidate gene. In our study we analyzed promoter polymorphism -1019C>G on 323 suicide victims and 190 controls (all of Slovenian origin), taking into account sex, suicide method, and in case of suicide victims also stressful life events. Differences in the distributions of genotype and allele frequencies were not statistically significant between suicide victims and control group, and the same was found for distributions according to sex and suicide method. For 62 suicide victims information about stressful life events in the month prior to the suicide and in childhood was provided. For analysis we combined CG/GG genotypes and compared them to the CC genotype. More stressful life events in the month prior to the suicide were reported for the subgroup with CC genotype (mean number of events = 2.53; SD = 1.50) in comparison to subgroup with CG/GG genotypes (mean number of events = 1.58; SD = 1.32; P < 0.05). However, subgroups of suicide victims with CC or CG/GG genotypes did not differ regarding numbers of reported stressful life events in childhood (P > 0.05). Our study provides no evidence for the implication of HTR1A promoter polymorphism in suicide in general, but it suggests further studies that would take into account the interconnected network of suicide completion, genetic background and stress, beside other risk factors.

摘要

血清素能系统在自杀及自杀未遂中的作用已被探讨多年。哺乳动物大脑中最丰富的血清素受体之一是1A受体(5-HT1A);迄今为止,对其多态性与自杀关系的研究结果非常不一致。有观点认为,G等位基因会抑制HTR1A自身受体的表达,从而减少可能导致抑郁和自杀的血清素能神经传递,这使得启动子多态性-1019C>G成为一个非常有前景的候选基因。在我们的研究中,我们分析了323名自杀受害者和190名对照者(均为斯洛文尼亚血统)的启动子多态性-1019C>G,同时考虑了性别、自杀方式,对于自杀受害者还考虑了生活应激事件。自杀受害者与对照组之间基因型和等位基因频率分布的差异无统计学意义,按性别和自杀方式的分布情况也是如此。对于62名自杀受害者,提供了自杀前一个月及童年时期生活应激事件的信息。为了进行分析,我们将CG/GG基因型合并,并与CC基因型进行比较。与CG/GG基因型亚组(平均事件数=1.58;标准差=1.32;P<0.05)相比,CC基因型亚组在自杀前一个月报告的生活应激事件更多(平均事件数=2.53;标准差=1.50)。然而,CC或CG/GG基因型的自杀受害者亚组在童年时期报告的生活应激事件数量上没有差异(P>0.05)。我们的研究总体上没有为HTR1A启动子多态性与自杀有关提供证据,但它建议进一步开展研究,除其他风险因素外,还要考虑自杀完成、遗传背景和应激之间相互关联的网络。

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