创伤后应激障碍的遗传易感性：催产素受体、视黄酸受体相关孤儿受体A和大麻素受体1基因的分析

Genetic Susceptibility to Posttraumatic Stress Disorder: Analyses of the Oxytocin Receptor, Retinoic Acid Receptor-Related Orphan Receptor A and Cannabinoid Receptor 1 Genes.

作者信息

Kučukalić Sabina, Ferić Bojić Elma, Babić Romana, Avdibegović Esmina, Babić Dragan, Agani Ferid, Jakovljević Miro, Kučukalić Abdulah, Bravo Mehmedbašić Alma, Šabić Džananović Emina, Marjanović Damir, Kravic Nermina, 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, Džubur Kulenović Alma

机构信息

Department of Psychiatry, Clinical Center University Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina,

出版信息

Psychiatr Danub. 2019 Jun;31(2):219-226. doi: 10.24869/psyd.2019.219.

DOI:10.24869/psyd.2019.219

PMID:31291229

Abstract

BACKGROUND

Exposure to life-threatening events is common and everyone will most likely experience this type of trauma during their lifetime. Reactions to these events are highly heterogeneous and seems to be influenced by genes as well. Some individuals will develop posttraumatic stress disorder (PTSD), while others will not. In this study, our aim was to analyze the correlation between single nucleotide polymorphisms (SNPs) within the oxytocin receptor (OXTR) gene (rs53576 and rs2254298), the RAR-related orphan receptor A (RORA) gene (rs8042149) and the cannabinoid receptor 1 (CNR1) gene (rs1049353) and PTSD. All candidate genes have been previously associated with stress related disorders and the reaction to traumatic events.

SUBJECTS AND METHODS

Participants (N=719) have been exposed to war-related trauma during the war in South-Eastern Europe (Bosnia and Herzegovina, Croatia and Kosovo). We correlated the presence and absence of current and lifetime PTSD as well as PTSD severity (Clinician Administered PTSD scale (CAPS)) and current psychopathology (Brief Symptom Inventory (BSI) score) with the mentioned SNPs. DNA was isolated from whole blood and genotyped for OXTR rs2254298 and rs53576 following previously published protocols, for RORA rs8042149 via PCR-RFLP and CNR1 rs1049353 via KASP.

RESULTS

Nominally significant results were found for OXTR rs53576 in connection with the CAPS and BSI scores within lifetime PTSD patients. The additive allelic model indicated that G allele carriers achieved lower CAPS (p=0.0090) and BSI (p=0.0408) scores than participants carrying one or two copies of the A allele. These results did not withstand correction for multiple tests. No significant results were observed for OXTR rs2254298, RORA rs8042149 and CNR1 rs1049353 although the results for RORA showed a slight tendency that rs8042149 may influence the level of BSI scores in current PTSD patients.

CONCLUSIONS

This study points to a role of the OXTR gene in PTSD and the related psychopathology following war related trauma.

摘要

背景

暴露于危及生命的事件很常见，每个人一生中很可能都会经历这类创伤。对这些事件的反应高度异质，似乎也受基因影响。一些人会患上创伤后应激障碍（PTSD），而另一些人则不会。在本研究中，我们的目的是分析催产素受体（OXTR）基因（rs53576和rs2254298）、视黄酸相关孤儿受体A（RORA）基因（rs8042149）和大麻素受体1（CNR1）基因（rs1049353）内的单核苷酸多态性（SNP）与PTSD之间的相关性。所有候选基因先前都已与应激相关障碍及对创伤事件的反应相关联。

对象与方法

参与者（N = 719）在东南欧战争（波斯尼亚和黑塞哥维那、克罗地亚和科索沃）期间暴露于与战争相关的创伤。我们将当前和终生PTSD的有无、PTSD严重程度（临床医生评定的PTSD量表（CAPS））以及当前精神病理学（简明症状量表（BSI）评分）与上述SNP进行关联分析。从全血中分离DNA，并按照先前发表的方案对OXTR rs2254298和rs53576进行基因分型，通过聚合酶链反应 - 限制性片段长度多态性（PCR - RFLP）对RORA rs8042149进行基因分型，通过竞争性等位基因特异性PCR（KASP）对CNR1 rs1049353进行基因分型。

结果

在终生PTSD患者中，发现OXTR rs53576与CAPS和BSI评分存在名义上的显著关联。加性等位基因模型表明，与携带一个或两个A等位基因拷贝的参与者相比，G等位基因携带者的CAPS评分（p = 0.0090）和BSI评分（p = 0.0408）更低。这些结果在多重检验校正后不成立。对于OXTR rs2254298、RORA rs8042149和CNR1 rs1049353未观察到显著结果，尽管RORA的结果显示rs8042149可能影响当前PTSD患者的BSI评分水平有轻微趋势。