5-羟色胺受体1A（HTR1A）和色氨酸羟化酶2（TPH2）基因的等位基因变异在创伤后应激障碍（PTSD）发生发展中的作用

Role of the Allelic Variation in the 5-Hydroxytryptamine Receptor 1A (HTR1A) and the Tryptophan Hydroxylase 2 (TPH2) Genes in the Development of PTSD.

作者信息

Goçi Uka Afërdita, Agani Ferid, Blyta Afrim, Hoxha Blerina, Haxhibeqiri Shpend, Haxhibeqiri Valdete, Sabic Dzananovic Emina, Kucukalic Sabina, Bravo Mehmedbasic Alma, Kucukalic Abdulah, Dzubur-Kulenovic Alma, Feric Bojic Elma, Marjanovic Damir, Kravic Nermina, Avdibegovic Esmina, Muminovic Umihanic Mirnesa, Jaksic Nenad, Cima Franc Ana, Rudan Dusko, Jakovljevic Miro, Babic Romana, Pavlovic Marko, Babic Dragan, Aukst Margetic Branka, Bozina Nada, Sinanovic Osman, Ziegler Christiane, Warrings Bodo, Domschke Katharina, Deckert Jürgen, Wolf Christiane

机构信息

Department of Psychiatry, University Clinical Centre of Kosovo, Str, Hile Mosi, nr 11, 10000 Prishtina, Kosovo,

出版信息

Psychiatr Danub. 2019 Jun;31(2):256-262. doi: 10.24869/psyd.2019.256.

DOI:10.24869/psyd.2019.256

PMID:31291234

Abstract

BACKGROUND

Post-traumatic stress disorder (PTSD) is a stress related disorder which can occur in an individual after exposure to a traumatic event. It most commonly co-occurs with depression. The two disorders share not only overlapping symptoms, but also genetic diathesis. The aim of this study was to investigate the potential role of single nucleotide polymorphisms (SNPs) of the two serotonergic candidate genes 5-hydroxytryptamine receptor 1A (HTR1A) and tryptophan hydroxylase 2 (TPH2) in the pathogenesis of PTSD and comorbid psychopathology.

SUBJECTS AND METHODS

719 (487 males, 232 females) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Herzegovina, Kosovo and Croatia were included in the study. The Sociodemographic questionnaire, Mini International Neuropsychiatric Interview (M.I.N.I.), Clinician Administered PTSD Scale (CAPS) and Brief Symptom Inventory (BSI) were used to collect clinical data. The SNPs rs6295 (HTR1A), rs11178997 and rs1386494 (TPH2) were investigated for their association with PTSD and comorbid psychopathology.

RESULTS

A nominal significant association was found between the BSI total score in Lifetime PTSD with the SNP rs6295 of the HTR1A gene. The best result was seen in the dominant model (P=0.018), with the minor allele (C) being the risk allele. Several BSI subscores were also associated with the minor (C) allele in Lifetime PTSD. No association was found for the TPH2 SNPs rs11178997 and rs1386494 in relation to PTSD or comorbid psychopathology.

CONCLUSIONS

Our findings suggest that rs6295 in the HTR1A gene may contribute to the psychopathology of PTSD.

摘要

背景

创伤后应激障碍（PTSD）是一种与应激相关的障碍，个体在经历创伤事件后可能会发生。它最常与抑郁症共病。这两种障碍不仅有重叠的症状，还存在遗传易感性。本研究的目的是调查两个血清素能候选基因5-羟色胺受体1A（HTR1A）和色氨酸羟化酶2（TPH2）的单核苷酸多态性（SNP）在PTSD发病机制及共病精神病理学中的潜在作用。

对象与方法

本研究纳入了719名（487名男性，232名女性）在1991年至1999年期间在波斯尼亚和黑塞哥维那、科索沃及克罗地亚经历过与战争相关创伤的参与者。使用社会人口学问卷、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）收集临床数据。研究了SNP rs6295（HTR1A）、rs11178997和rs1386494（TPH2）与PTSD及共病精神病理学的关联。

结果

在终身PTSD患者中，发现HTR1A基因的SNP rs6295与BSI总分之间存在名义上的显著关联。在显性模型中结果最佳（P = 0.018），次要等位基因（C）为风险等位基因。终身PTSD患者的几个BSI子分数也与次要（C）等位基因相关。未发现TPH2基因的SNP rs11178997和rs1386494与PTSD或共病精神病理学有关联。