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自杀行为的遗传易感性:两个巴尔干人群中GRIN2B、GABRG2和ODC1基因变异与自杀未遂及自杀身亡的关系

Genetic predisposition of suicidal behavior: variants in GRIN2B, GABRG2, and ODC1 genes in attempted and completed suicide in two Balkan populations.

作者信息

Karanović Jelena, Beraković Doroteja, Katrašnik Mojca, Šalamon Arčan Iris, Pantović-Stefanović Maja, Radenković Lana, Garai Nemanja, Ivković Maja, Savić-Pavićević Dušanka, Zupanc Tomaž, Videtič Paska Alja

机构信息

Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Studentski trg 16, PO box 43, Belgrade, 11000, Serbia.

Laboratory for Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444A, Belgrade, 11042, Serbia.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2025 Jun;275(4):1221-1230. doi: 10.1007/s00406-024-01895-9. Epub 2024 Sep 19.

Abstract

Completed suicide accounts for over 700,000 deaths worldwide annually, while attempted suicide is 20 times more frequent. Genetic background is an important factor contributing to suicidal behavior, including candidate genes in glutamate, γ-aminobutyric acid (GABA), and polyamine systems. Our aim was to differentiate genetic predispositions underlying different types of suicidal behavior, attempted and completed suicide, in two Balkan populations. Analysis of variants in the genes GRIN2B (rs2268115 and rs220557), GABRG2 (rs424740), and ODC1 (rs1049500 and rs2302614) was performed on a study sample including 173 suicide attempters with comorbid psychiatric disorders, 216 non-suicidal psychiatric patients and 172 healthy controls from Serbia, and 333 suicide completers and 356 non-suicidal autopsy controls from Slovenia. CA genotype of rs220557 in GRIN2B gene increased the risk for completed suicide (P = 0.021), and violent suicide (P = 0.037), compared to controls. In ODC1 gene, CA genotype of rs2302614 decreased the risk for completed suicide compared to suicide attempt (P = 0.012). Marginally, AC haplotype for variants rs1049500-rs2302614 in ODC1 gene decreased the risk for completed suicide compared to suicide attempt (P = 0.052). Specific genetic variants of glutamate and polyamine systems are differently distributed among diverse suicidal phenotypes, providing further information on the implication of these systems in suicidality.

摘要

全球每年有超过70万人死于自杀,而自杀未遂的发生率则是自杀死亡的20倍。遗传背景是导致自杀行为的一个重要因素,包括谷氨酸、γ-氨基丁酸(GABA)和多胺系统中的候选基因。我们的目的是在两个巴尔干半岛人群中区分不同类型自杀行为(自杀未遂和自杀死亡)背后的遗传易感性。对GRIN2B基因(rs2268115和rs220557)、GABRG2基因(rs424740)和ODC1基因(rs1049500和rs2302614)的变异进行了分析,研究样本包括来自塞尔维亚的173名伴有精神疾病的自杀未遂者、216名非自杀性精神疾病患者和172名健康对照,以及来自斯洛文尼亚的333名自杀死亡者和356名非自杀性尸检对照。与对照组相比,GRIN2B基因rs220557的CA基因型增加了自杀死亡风险(P = 0.021)和暴力自杀风险(P = 0.037)。在ODC1基因中,与自杀未遂相比,rs2302614的CA基因型降低了自杀死亡风险(P = 0.012)。ODC1基因中rs1049500 - rs2302614变异的AC单倍型与自杀未遂相比,略微降低了自杀死亡风险(P = 0.052)。谷氨酸和多胺系统的特定基因变异在不同的自杀表型中分布不同,为这些系统在自杀行为中的作用提供了更多信息。

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