Association of single nucleotide variants rs34532313 of the MTNR1A gene and rs10830963 of the MTNR1B gene with suicidal risk in alcohol dependence syndrome and insomnia

I. S. Efremov, A. Asadullin, E. Akhmetova, L. R. Migranova, V. Yuldashev, N. A. Marfina, E. R. Kunafina, M. N. Gilmiyarova, D. H. Kalimullina, S. U. Tuktarova, E. Y. Sidorova, V. Dobrodeeva, R. Nasyrova
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引用次数: 1

Abstract

Background: Suicidal behaviour is the leading cause of mortality from external causes at all ages worldwide. More than a million people commit completed suicide each year. According to the World Health Organisation, 25-50% of suicide victims suffered from alcohol and other substance use disorders, 22% of all suicide deaths were attributable to alcohol use (WHO, 2014). Several papers have suggested potential associations of insomnia and increased suicide risk in patients with alcoholism. We hypothesise that mutations in melatonin receptor genes may be associated with suicide risk in patients with alcoholism.Methods. The Insomnia Severity Index (ISI) was used as a tool to assess the presence and severity of insomnia. The Columbia Suicide Severity Rating Scale (C-SSRS) was used as a method to examine suicidal behavior. Genotyping of MTNR1A (rs34532313), MTNR1B (rs10830963) genes was performed using real-time polymerase chain reaction (RT-PCR). A comparative genetic study of two groups of patients was carried out: the first group, patients with alcohol dependence syndrome (F10.2); the second group, patients with alcohol dependence syndrome (F10.2) and insomnia, which persisted 7-14 days after starting alcohol withdrawal therapy.Results. Suicidal thoughts and a history of auto-aggressive behaviour were more common in subjects with insomnia in the post-withdrawal period. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were more likely to have suicidal thoughts and a history of suicide attempts in a genetic study of patients with insomnia.Conclusions. Our study found that the TT genotype of the MTNR1A gene (rs34532313) is a genetic marker of suicidal behaviour risk in patients with insomnia in the post-withdrawal period. However, the same pattern was not observed in patients without insomnia.
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MTNR1A基因单核苷酸变异rs34532313和MTNR1B基因rs10830963与酒精依赖综合征和失眠患者自杀风险的关联
背景:自杀行为是全世界各年龄段外因死亡的主要原因。每年有超过一百万人自杀。据世界卫生组织称,25-50%的自杀受害者患有酒精和其他物质使用障碍,22%的自杀死亡可归因于酒精使用(世卫组织,2014年)。有几篇论文提出了酗酒患者失眠和自杀风险增加之间的潜在联系。我们假设褪黑激素受体基因的突变可能与酗酒患者的自杀风险有关。失眠症严重程度指数(ISI)被用作评估失眠症存在和严重程度的工具。采用哥伦比亚自杀严重程度评定量表(C-SSRS)检查自杀行为。采用实时聚合酶链反应(RT-PCR)对MTNR1A (rs34532313)、MTNR1B (rs10830963)基因进行分型。对两组患者进行比较遗传学研究:第一组为酒精依赖综合征患者(F10.2);第二组为酒精依赖综合征(F10.2)和失眠患者,在开始戒酒治疗后持续7-14天。在戒断期失眠症患者中,自杀念头和自我攻击行为史更为常见。MTNR1A基因(rs34532313) TT基因型携带者在失眠症患者中更容易有自杀念头和自杀未遂史。我们的研究发现MTNR1A基因(rs34532313)的TT基因型是戒断期失眠症患者自杀行为风险的遗传标记。然而,在没有失眠的患者中没有观察到相同的模式。
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