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促肾上腺皮质激素释放激素 1 型受体基因(CRHR1)变体可预测儿科创伤患者创伤后应激障碍的发病和病程。

Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients.

机构信息

Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, 23298-0126, USA.

出版信息

Dis Markers. 2011;30(2-3):89-99. doi: 10.3233/DMA-2011-0761.

Abstract

Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n=103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.

摘要

创伤后应激障碍(PTSD)是一种常见且使人丧失能力的焦虑障碍,可能发生在经历潜在创伤性生活事件之后。PTSD 具有中度遗传性,但尚未确定可解释这种遗传性的少数特定分子变异。调节下丘脑-垂体-肾上腺(HPA)轴的基因,如促肾上腺皮质激素释放激素 1 型受体基因(CRHR1),与创伤应激相关表型有关,但尚未在 PTSD 方面进行研究。本研究旨在通过对儿科创伤患者(n=103)的前瞻性研究来检查 CRHR1 基因中的 9 个单核苷酸多态性(SNP)与创伤后应激症状之间的关系,这些患者在受伤后的急性期首先在医院进行评估。结果表明,多个 SNP 在单变量水平上与急性症状相关,在进行多重检验校正后,rs12944712 与急性 PTSD 症状显著相关。纵向潜在增长曲线分析表明,rs12944712 也与急性症状水平和随时间推移的症状轨迹有关。本研究为 CRHR1 在青少年经历潜在创伤性事件后应激反应中的作用提供了更多支持。需要注意的是,这项研究的样本量较小,因此统计能力较低;因此,应慎重考虑本研究的结果。尽管结果还不是定论,但这项研究的结果表明,该基因的变异如何与青少年对创伤性事件暴露的反应有关,值得进一步开展研究。

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