神经肽Y和脑源性神经营养因子基因变异与创伤后应激障碍的关联

Associations of Gene Variations in Neuropeptide Y and Brain Derived Neurotrophic Factor Genes with Posttraumatic Stress Disorder.

作者信息

Ferić Bojić Elma, Kučukalić Sabina, Džubur Kulenović Alma, Avdibegović Esmina, Babić Dragan, Agani Ferid, Jakovljević Miro, Kučukalić Abdulah, Bravo Mehmedbašić Alma, Šabić Džananović Emina, Kravic Nermina, Babić Romana, Pavlović Marko, Aukst Margetic Branka, Jaksic Nenad, Cima Franc Ana, Rudan Dusko, Haxhibeqiri Shpend, Goci Uka Aferdita, Hoxha Blerina, Haxhibeqiri Valdete, Muminović Umihanić Mirnesa, Sinanović Osman, Božina Nada, Ziegler Christiane, Wolf Christiane, Warrings Bodo, Domschke Katharina, Deckert Jürgen, Marjanović Damir

机构信息

International Burch University, Department of Genetics and Bioengineering, Francuske revolucije bb, 71000 Sarajevo, Bosnia and Herzegovina,

出版信息

Psychiatr Danub. 2019 Jun;31(2):227-234. doi: 10.24869/psyd.2019.227.

DOI:10.24869/psyd.2019.227

PMID:31291230

Abstract

BACKGROUND

Individuals who are exposed to traumatic events are at an increased risk of developing posttraumatic stress disorder (PTSD), a condition during which an individual's ability to function is impaired by emotional responses to memories of those events. The gene coding for neuropeptide Y (NPY) and the gene coding for brain-derived neurotrophic factor (BDNF) are among the number of candidate gene variants that have been identified as potential contributors to PTSD. The aim of this study was to investigate the association between NPY and BDNF and PTSD in individuals who experienced war-related trauma in the South Eastern Europe (SEE) conflicts (1991-1999).

SUBJECTS AND METHODS

This study included participants with current and remitted PTSD and healthy volunteers (N=719, 232 females, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administered PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). DNA was isolated from whole blood and genotyped for NPY rs5574 via PCR - RFLP and NPY rs16147 and BDNF rs6265 using the KASP assay.

RESULTS

Tests for deviation from Hardy-Weinberg equilibrium showed no significant results. Analyses at the categorical level yielded no associations between the affected individuals and all three SNPs when compared to controls. Within lifetime PTSD patients, the major alleles of both NPY variants showed a nominally significant association with higher CAPS scores (p=0.007 and p=0.02, respectively). Also, the major allele of rs5574C>T was associated with higher BSI scores with a nominal significance among current PTSD patients (p=0.047). The results did not withstand a Bonferroni adjustment (α=0.002).

CONCLUSION

Nominally significant associations between NPY polymorphisms and PTSD susceptibility were found that did not withstand Bonferroni correction.

摘要

背景

遭受创伤性事件的个体患创伤后应激障碍（PTSD）的风险增加，在这种情况下，个体的功能能力会因对这些事件记忆的情绪反应而受损。编码神经肽Y（NPY）的基因和编码脑源性神经营养因子（BDNF）的基因是已被确定为PTSD潜在促成因素的众多候选基因变体之一。本研究的目的是调查在东南欧（SEE）冲突（1991 - 1999年）中经历与战争相关创伤的个体中，NPY和BDNF与PTSD之间的关联。

对象与方法

本研究纳入了患有当前和缓解期PTSD的参与者以及健康志愿者（N = 719，女性232名，男性487名），他们是在2013年至2015年期间在东南欧（SEE）-PTSD研究框架内招募的。心理测量方法包括迷你国际神经精神病学访谈（M.I.N.I.）、临床医生管理的PTSD量表（CAPS）和简明症状量表（BSI）。从全血中分离DNA，并通过聚合酶链反应 - 限制性片段长度多态性（PCR - RFLP）对NPY rs5574进行基因分型，使用竞争性等位基因特异性PCR（KASP）分析对NPY rs16147和BDNF rs6265进行基因分型。

结果

哈迪 - 温伯格平衡偏离检验未显示显著结果。与对照组相比，在分类水平上的分析未发现受影响个体与所有三个单核苷酸多态性（SNP）之间存在关联。在终生PTSD患者中，两种NPY变体的主要等位基因与较高的CAPS评分显示出名义上的显著关联（分别为p = 0.007和p = 0.02）。此外，rs5574C>T的主要等位基因与当前PTSD患者中较高的BSI评分相关，具有名义上的显著性（p = 0.047）。这些结果未通过邦费罗尼校正（α = 0.002）。