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创伤后应激障碍候选基因研究:城市暴力后基因编码 5-羟色胺转运体、多巴胺转运体和脑源性神经营养因子的关联分析。

Candidate-gene approach in posttraumatic stress disorder after urban violence: association analysis of the genes encoding serotonin transporter, dopamine transporter, and BDNF.

机构信息

Departamento de Psiquiatria, Universidade Federal de São Paulo, Rua Botucatu 431, Vila Clementino, São Paulo, CEP 04023-061, São Paulo, Brazil.

出版信息

J Mol Neurosci. 2011 May;44(1):59-67. doi: 10.1007/s12031-011-9513-7. Epub 2011 Mar 29.

Abstract

Posttraumatic stress disorder (PTSD) is a prevalent, disabling anxiety disorder marked by behavioral and physiologic alterations which commonly follows a chronic course. Exposure to a traumatic event constitutes a necessary, but not sufficient, factor. There is evidence from twin studies supporting a significant genetic predisposition to PTSD. However, the precise genetic loci still remain unclear. The objective of the present study was to identify, in a case-control study, whether the brain-derived neurotrophic factor (BDNF) val66met polymorphism (rs6265), the dopamine transporter (DAT1) three prime untranslated region (3'UTR) variable number of tandem repeats (VNTR), and the serotonin transporter (5-HTTPRL) short/long variants are associated with the development of PTSD in a group of victims of urban violence. All polymorphisms were genotyped in 65 PTSD patients as well as in 34 victims of violence without PTSD and in a community control group (n = 335). We did not find a statistical significant difference between the BDNF val66met and 5-HTTPRL polymorphism and the traumatic phenotype. However, a statistical association was found between DAT1 3'UTR VNTR nine repeats and PTSD (OR = 1.82; 95% CI, 1.20-2.76). This preliminary result confirms previous reports supporting a susceptibility role for allele 9 and PTSD.

摘要

创伤后应激障碍(PTSD)是一种普遍存在的、使人丧失能力的焦虑障碍,其特征为行为和生理改变,通常呈慢性病程。创伤事件的暴露是一个必要但不充分的因素。来自双胞胎研究的证据支持 PTSD 存在显著的遗传易感性。然而,确切的遗传位点仍不清楚。本研究的目的是在病例对照研究中确定脑源性神经营养因子(BDNF)val66met 多态性(rs6265)、多巴胺转运体(DAT1)三磷酸未翻译区(3'UTR)可变串联重复(VNTR)和 5-羟色胺转运体(5-HTTPRL)短/长变体是否与一组城市暴力受害者 PTSD 的发生有关。所有多态性均在 65 例 PTSD 患者、34 例无 PTSD 的暴力受害者和 335 名社区对照组中进行了基因分型。我们没有发现 BDNF val66met 和 5-HTTPRL 多态性与创伤表型之间存在统计学显著差异。然而,我们发现 DAT1 3'UTR VNTR 九重复与 PTSD 之间存在统计学关联(OR = 1.82;95%CI,1.20-2.76)。这一初步结果证实了先前支持等位基因 9 与 PTSD 易感性作用的报告。

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