p75NTR基因标签SNPs在PTSD易患性中的作用与机制研究

With the increasing of unexpected traumatic event, the incidence of post-traumatic stress disorder (PTSD) increased in recent years, which has been paid close attention with the characteristic of high incidence, long course, difficult to be cared, and seriously impact on people's physical and mental health. The rule of PTSD occurrence is based on its unique genetic background, study of the correlation between the occurrence and the susceptibility of PTSD on the genetic background, conducive to early detection of PTSD susceptible individuals, personalized warning, timely and effective intervention, and reduction of PTSD prevalence. p75NTR, with neuronal cell apoptotic effects and regulation of synaptic plasticity, have been shown to be involved in the occurrence of PTSD, may be a new therapeutic target for PTSD. The gene polymorphisms of p75NTR gene have been indicated to be associated with comorbidity of PTSD such as depressive disorder, for which they may be relevant with PTSD in the genetic susceptibility. In this study, HapMap database will be used to construct haplotype block of p75NTR entire gene in Chinese Han people, and the risk of tag SNPs and haplotype to PTSD will be selected by using bioinformatics technology. The biological function of the selected tag SNPs and haplotype will be detected in vitro, and the susceptibility to PTSD and the mechanism will be further investigated by using clinical relevance study and animal experiments. The present study will provide effective genetic markers for the early warning, diagnosis, and personalized therapy for PTSD.

随着意外创伤性事件的增多，创伤后应激障碍 (PTSD)的发生率逐年增加，已成为全球备受关注的一种高发病，其病程长，治愈率低，危害性强。PTSD的发生有其特有的基因背景，从基因背景上深入研究PTSD的发生规律及其与PTSD易患性的关系，有利于易感个体的早期发现、个性化预警、有效干预，减少发生率。研究表明p75NTR可通过促凋亡效应及调节突触可塑性介导PTSD的发生，是介导PTSD发生的一个新靶点。p75NTR基因多态性与PTSD的共病如抑郁症等密切相关，推测其可能与PTSD的遗传易患性有关。基于此本研究以中国汉族人群为研究对象，利用HapMap数据库及生物信息学技术，在p75NTR全基因范围内筛选具有预测PTSD风险性的标志性SNPs及单倍型，体外检测其生物学功能并结合临床关联分析及动物实验，进一步探讨其在PTSD易患性中的作用与机制，为PTSD的早期预警诊断及个性化治疗提供有效的基因标志。

创伤后应激障碍 (posttraumatic stress disorder, PTSD)的发生有其特有的基因背景，从基因背景上深入研究PTSD的发生规律及其与PTSD易患性的关系，有利于易感个体的早期发现、个性化预警、有效干预，减少发生率。研究表明p75神经营养素受体（p75 neurotrophin receptor，p75NTR）可能通过促凋亡效应及调节突触可塑性介导PTSD的发生，且p75NTR基因多态性与PTSD的共病如抑郁症等密切相关，推测其可能与PTSD的遗传易患性有关。基于此本研究以中国汉族人群为研究对象，利用HapMap数据库及生物信息学技术，在p75NTR全基因范围内筛选具有预测PTSD风险性的标志性SNPs及单倍型，并结合临床关联分析及动物实验，进一步探讨其生物学功能及在PTSD易患性中的作用与机制。结果表明，在筛选的12个标签SNPs中，结合以往研究报道，有5个SNPs可能影响p75NTR功能，但只有rs2072446(C15040T)与PTSD的发生存在一定的关联，且野生型与突变型相比更易患PTSD。该结果在大鼠及p75NTR基因敲除小鼠中得到进一步验证，从而为PTSD的早期预警诊断及个性化治疗提供了有效的基因标志。