...
首页> 外文期刊>Archives of general psychiatry. >Association of genetic variants in the neurotrophic receptor-encoding gene NTRK2 and a lifetime history of suicide attempts in depressed patients.
【24h】

Association of genetic variants in the neurotrophic receptor-encoding gene NTRK2 and a lifetime history of suicide attempts in depressed patients.

机译:协会的遗传变异神经营养receptor-encoding NTRK2和基因终生抑郁自杀企图的历史病人。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       

摘要

CONTEXT: A consistent body of evidence supports a role of reduced neurotrophic signaling in the pathophysiology of major depressive disorder (MDD) and suicidal behavior. Especially in suicide victims, lower postmortem brain messenger RNA and protein levels of neurotrophins and their receptors have been reported. OBJECTIVE: To determine whether the brain-derived neurotrophic factor (BDNF) gene or its high-affinity receptor gene, receptor tyrosine kinase 2 (NTRK2), confer risk for suicide attempt (SA) and MDD by investigating common genetic variants in these loci. DESIGN: Eighty-three tagging single-nucleotide polymorphisms (SNPs) covering the genetic variability of these loci in European populations were assessed in a case-control association design. SETTING: Inpatients and screened control subjects. PARTICIPANTS: The discovery sample consisted of 394 depressed patients, of whom 113 had SA, and 366 matched healthy control subjects. The replication studies comprised 744 German patients with MDD and 921 African American nonpsychiatric clinic patients, of whom 152 and 119 were positive for SA, respectively. INTERVENTIONS: Blood or saliva samples were collected from each participant for DNA extraction and genotyping. MAIN OUTCOME MEASURES: Associations of SNPs in BDNF and NTRK2 with SA and MDD. RESULTS: Independent SNPs within NTRK2 were associated with SA among depressed patients of the discovery sample that could be confirmed in both the German and African American replication samples. Multilocus interaction analysis revealed that single SNP associations within this locus contribute to the risk of SA in a multiplicative and interactive fashion (P = 4.7 x 10(-7) for a 3-SNP model in the combined German sample). The effect size was 4.5 (95% confidence interval, 2.1-9.8) when patients carrying risk genotypes in all 3 markers were compared with those without any of the 3 risk genotypes. CONCLUSIONS: Our results suggest that a combination of several independent risk alleles within the NTRK2 locus is associated with SA in depressed patients, further supporting a role of neurotrophins in the pathophysiology of suicide.
机译:背景:一致的证据支持减少神经营养信号的作用重度抑郁症的病理生理学(MDD)和自杀行为。自杀者,降低后期大脑信使RNA和蛋白质的神经营养因子和水平受体的报告。确定脑源性神经营养因子(BDNF)基因或其高亲和性受体基因、受体酪氨酸激酶2 (NTRK2)企图自杀的风险(SA)和MDD调查这些常见的基因变异位点。单核苷酸多态性(snp)覆盖这些位点的遗传变异在欧洲病例对照人群进行评估协会设计。对照组的筛选。发现样本由394年抑郁患者,其中113 SA和366匹配健康对照组。由744年德国MDD和921名患者非裔美国人非精神性诊所的病人,其中152年和119年为SA是积极的,分别。从每个参与者收集的样本DNA提取和基因分型。措施:协会BDNF和NTRK2的snpSA和MDD。NTRK2与SA在抑郁有关病人的样本,可以发现证实了在德国和非裔美国人复制样品。分析显示,SNP关联在这个轨迹有助于SA的风险乘法和互动方式(P = 4.7)x 10 (7) 3-SNP模型合并后的德国人样本)。区间,2.1 - -9.8)当病人携带的风险在所有3标记与基因型那些没有任何3基因型风险。结论:我们的研究结果表明,a几个独立的风险等位基因的组合在NTRK2轨迹与SA抑郁症患者,进一步支持的角色神经营养因子在自杀的病理生理学。

著录项

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号