FKBP5和CRHR1基因多态性与战争相关创伤后应激障碍的候选基因关联研究

A Candidate Gene Association Study of FKBP5 and CRHR1 Polymorphisms in Relation to War-Related Posttraumatic Stress Disorder.

作者信息

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

机构信息

Department of Psychiatry, University Hospital Centre Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia,

出版信息

Psychiatr Danub. 2019 Jun;31(2):269-275. doi: 10.24869/psyd.2019.269.

DOI:10.24869/psyd.2019.269

PMID:31291236

Abstract

BACKGROUND

Posttraumatic stress disorder (PTSD) is a highly frequent and disabling psychiatric condition among war-affected populations. The FK506-binding protein 5 (FKBP5) gene and the corticotropin-releasing hormone receptor 1 (CRHR1) gene have previously been implicated in an elevated risk of peritraumatic dissociation and PTSD development. Our aim was to investigate the association between FKBP5 and CRHR1 genotypes and PTSD diagnosis and severity among individuals who were affected by the Balkan wars during the 1990s.

SUBJECTS AND METHODS

This study included participants with current PTSD, remitted PTSD and healthy volunteers (N=719, 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 Administrated PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). FKBP5 rs1360780 and CRHR1 rs17689918 genotypes were determined using a KASP genotyping assay.

RESULTS

Tests for deviation from Hardy Weinberg equilibrium showed no significant results. Logistic and linear regression was used to examine the associations between the FKBP5 SNP rs1360780 and the CRHR1 SNP rs17689918 with PTSD diagnosis and severity, as well as general psychiatric symptom severity, separately for current and remitted PTSD patients. There were nominally significant associations under a dominant model between the rs1360780 C allele and PTSD diagnosis as well as symptom severity, which however, were not significant anymore after Bonferroni adjustment (α=0.002). For CRHR1 rs17689918 no significant associations were detected.

CONCLUSION

We found nominally, but not Bonferroni corrected significant associations between the FKBP5 polymorphism rs1360780 and PTSD susceptibility among individuals affected by the Balkan wars. For elucidating this gene's real resilience/vulnerability potential, environmental influences should be taken into account.

摘要

背景

创伤后应激障碍（PTSD）在受战争影响的人群中是一种非常常见且使人致残的精神疾病。此前，FK506结合蛋白5（FKBP5）基因和促肾上腺皮质激素释放激素受体1（CRHR1）基因被认为与创伤期间解离增加及PTSD发病风险升高有关。我们的目的是调查20世纪90年代受巴尔干战争影响的个体中FKBP5和CRHR1基因分型与PTSD诊断及严重程度之间的关联。

对象与方法

本研究纳入了目前患有PTSD、已缓解的PTSD患者以及健康志愿者（N = 719，487名男性），这些参与者于2013年至2015年在东南欧（SEE）-PTSD研究框架内招募。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）。使用KASP基因分型检测法确定FKBP5 rs136,0780和CRHR1 rs17689918基因分型。

结果

哈迪-温伯格平衡偏离检验结果无统计学意义。采用逻辑回归和线性回归分别检验FKBP5单核苷酸多态性（SNP）rs1360780和CRHR1 SNP rs17689918与PTSD诊断及严重程度以及一般精神症状严重程度之间的关联，分析对象为目前患有PTSD和已缓解的PTSD患者。在显性模型下，rs1360780 C等位基因与PTSD诊断及症状严重程度之间存在名义上的显著关联，但经邦费罗尼校正（α = 0.002）后不再显著。对于CRHR1 rs17689918，未检测到显著关联。