Kao Wei-Tsung, Yang Ming-Chang, Lung For-Wey
Laboratory of Research, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; Department of Psychiatry, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan.
Laboratory of Research, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; Institute of Biological Science, National Sun Yet-sen University, Kaohsiung, Taiwan.
Neurosci Lett. 2017 Jan 18;638:204-210. doi: 10.1016/j.neulet.2016.12.043. Epub 2016 Dec 19.
Serotonin receptors, also known as 5-hydroxytryptamine receptors (HTRs), play a role in individuals' vulnerability to major depressive disorders (MDDs) and/or suicide attempts. In the first part of the study, we recruited 789 Taiwanese participants, which included 285 MDD patients, 191 MDD patients with a history of suicide attempts (MS), and 313 controls. The three groups were genotyped to identify HTR single nucleotide polymorphisms (SNPs) and we analyzed the correlations among the three groups. In the second part of the study, which involved a functional test of HTR1B allelic and haplotype variants, another 113 MDD patients were recruited. The rs6298-T allele was more frequent in the MS group than in the control group. The rs1923885-T allele occurred more frequently in the MS group than in the MDD group. Carriers of haplotype GT were estimated to have a 1.774-fold higher risk of suicide attempts. Younger age, alleles rs6296-C, rs6298-T and rs1923885-C, and haplotype CT were associated with a greater risk of MDD. Haplotypes GC and GT were directly associated with a lower risk of suicidal ideation. Haplotypes GC and GT also associated with higher levels of HTR1B mRNA, and haplotype GC was associated with extraversion, which caused a lower risk of suicidal ideation. The rs6296-C allele have directly and indirectly influenced a greater risk of suicidal ideation, which mediated by its negative effect on extraversion. Haplotype GT can be used to identify patients with a higher risk of suicide attempts. The rs6296-C allele lowered the level of HTR1B mRNA, causing individuals with MDD to display more hostility and aggressive behavior, which may lead to suicidal ideation.
血清素受体，也被称为5-羟色胺受体（HTRs），在个体患重度抑郁症（MDDs）和/或自杀未遂的易感性中起作用。在研究的第一部分，我们招募了789名台湾参与者，其中包括285名MDD患者、191名有自杀未遂史的MDD患者（MS）和313名对照者。对这三组进行基因分型以识别HTR单核苷酸多态性（SNPs），并分析三组之间的相关性。在研究的第二部分，涉及HTR1B等位基因和单倍型变体的功能测试，又招募了113名MDD患者。rs6298 - T等位基因在MS组中比在对照组中更常见。rs1923885 - T等位基因在MS组中比在MDD组中出现得更频繁。估计单倍型GT的携带者自杀未遂风险高1.774倍。年龄较小、rs6296 - C、rs6298 - T和rs1923885 - C等位基因以及单倍型CT与患MDD的风险更高相关。单倍型GC和GT与自杀意念风险较低直接相关。单倍型GC和GT也与较高水平的HTR1B mRNA相关，并且单倍型GC与外向性相关，这导致自杀意念风险较低。rs6296 - C等位基因直接和间接影响更高的自杀意念风险，这是由其对外向性的负面影响介导的。单倍型GT可用于识别自杀未遂风险较高患者。rs6296 - C等位基因降低了HTR1B mRNA水平，导致患有MDD的个体表现出更多敌意和攻击行为，这可能导致自杀意念。
