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青少年早期生活逆境与对反复应激的心血管反应:儿茶酚-O-甲基转移酶(COMT)基因rs4680多态性的调节作用

Early life adversity and cardiovascular responses to repeated stress among adolescents: Moderating role of COMT gene rs4680 polymorphism.

作者信息

Lü Wei, Ji Huayu, Li Yushan

机构信息

Shaanxi Key Laboratory of Behavior and Cognitive Neuroscience, Shaanxi Key Research Center for Children Mental and Behavior Health, School of Psychology, Shaanxi Normal University, China.

Shaanxi Key Laboratory of Behavior and Cognitive Neuroscience, Shaanxi Key Research Center for Children Mental and Behavior Health, School of Psychology, Shaanxi Normal University, China.

出版信息

Psychoneuroendocrinology. 2023 Apr;150:106029. doi: 10.1016/j.psyneuen.2023.106029. Epub 2023 Jan 20.

Abstract

BACKGROUND

Early life adversity (ELA) increases the risk of cardiovascular diseases through dysregulation of cardiovascular stress responses manifested by either exaggerated or blunted reactivity. The catechol-O-methyltransferase (COMT) gene rs4680 polymorphism has been identified in gene-environment interaction (G×E) studies to explain individual differences in the effects of ELA on physiological stress responses. However, little is known about whether ELA interacts with COMT gene rs4680 polymorphism to affect cardiovascular responses to repeated stress exposures.

OBJECTIVE

The current study examined the associations between ELA and cardiovascular responses to repeated stress exposures, and the moderating role of COMT rs4680 polymorphism in these associations.

METHODS

The childhood trauma questionnaire (CTQ) was administered to 359 junior school students who underwent a two-successive stress exposures protocol with continuous cardiovascular monitoring [heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP)] across four laboratory phases, and their saliva samples for deoxyribonucleic acid (DNA) genotyping were collected.

RESULTS

ELA was associated with blunted HR reactivity to the first and second stress exposures, blunted SBP reactivity to the first stress exposure, and attenuated SBP habituation to repeated stress exposures. Moreover, COMT rs4680 moderated these associations, such that the associations between ELA and blunted HR, SBP, and DBP reactivity to the first stress and disrupted DBP habituation to repeated stress exposures only existed in GA/AA genotype carriers but not in GG genotype carriers.

CONCLUSIONS

These findings suggest that the A allele of COMT rs4680 is vulnerable to the negative effects of ELA on the developmental dysregulation of stress physiological systems.

摘要

背景

早年生活逆境(ELA)通过心血管应激反应失调增加心血管疾病风险,这种失调表现为反应过度或反应迟钝。儿茶酚-O-甲基转移酶(COMT)基因rs4680多态性已在基因-环境相互作用(G×E)研究中被确定,以解释ELA对生理应激反应影响的个体差异。然而,关于ELA是否与COMT基因rs4680多态性相互作用以影响对反复应激暴露的心血管反应,人们知之甚少。

目的

本研究探讨ELA与对反复应激暴露的心血管反应之间的关联,以及COMT rs4680多态性在这些关联中的调节作用。

方法

对359名初中生进行儿童期创伤问卷(CTQ)调查,这些学生在四个实验室阶段接受了连续两次应激暴露方案,并进行持续的心血管监测[心率(HR)、收缩压和舒张压(SBP、DBP)],同时采集他们的唾液样本进行脱氧核糖核酸(DNA)基因分型。

结果

ELA与对第一次和第二次应激暴露的心率反应迟钝、对第一次应激暴露的收缩压反应迟钝以及对反复应激暴露的收缩压习惯化减弱有关。此外,COMT rs4680调节了这些关联,使得ELA与对第一次应激的心率、收缩压和舒张压反应迟钝以及对反复应激暴露的舒张压习惯化破坏之间的关联仅存在于GA/AA基因型携带者中,而不存在于GG基因型携带者中。

结论

这些发现表明,COMT rs4680的A等位基因易受ELA对应激生理系统发育失调的负面影响。

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