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儿童期创伤与载脂蛋白 E 相互作用,影响 HIV 感染者的神经认知功能。

Childhood trauma interacts with ApoE to influence neurocognitive function in women living with HIV.

机构信息

Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Drive, Tygerberg, 7505, South Africa.

出版信息

J Neurovirol. 2019 Apr;25(2):183-193. doi: 10.1007/s13365-018-0700-y. Epub 2018 Nov 26.

Abstract

HIV-associated neurocognitive disorder (HAND) describes a spectrum of behavioural, motor and cognitive disturbances that can occur secondary to HIV infection. Less severe forms of the disorder persist despite advances in antiretroviral medication efficacy and availability. Childhood trauma (CT) may predispose individuals to developing HAND. As genetic variation in human apolipoprotein E (ApoE) has been implicated in cognitive decline and may mediate the development of long-term health outcomes following CT, we investigated the influence of ApoE and CT on cognitive function in the context of HIV. One hundred twenty-eight HIV-positive Xhosa women completed the Childhood Trauma Questionnaire-Short Form (CTQ-SF) as well as the HIV Neurobehavioural Research Center neurocognitive test battery. rs7412 and rs429358 were genotyped using KASP assays, and this data was used to determine the ApoE isoform. Baseline differences in demographic and clinical variables according to CT exposure were calculated. Analysis of covariance was used to assess the contributions of CT and ApoE variants, as well as their interaction, to cognitive function. Eighty-eight participants reported experiencing CT. The rs7412 C allele protected against the harmful effect of CT on motor scores using an additive model. The interaction of ApoE ε4 and CT was associated with worse attention/working memory scores. ApoE ε4, alone and in combination with CT, is associated with poorer cognitive function. Further research into this gene-environment interaction may assist in identifying at-risk individuals for targeted interventions.

摘要

HIV 相关认知障碍(HAND)描述了一系列行为、运动和认知障碍,这些障碍可能继发于 HIV 感染。尽管抗逆转录病毒药物的疗效和可及性有所提高,但该疾病的较轻形式仍持续存在。童年创伤(CT)可能使个体易患 HAND。由于人类载脂蛋白 E(ApoE)的遗传变异与认知能力下降有关,并且可能介导 CT 后长期健康结果的发展,因此我们研究了 ApoE 和 CT 在 HIV 背景下对认知功能的影响。128 名 HIV 阳性的科萨妇女完成了儿童创伤问卷-短表(CTQ-SF)以及 HIV 神经行为研究中心神经认知测试组合。使用 KASP 测定法对 rs7412 和 rs429358 进行了基因分型,并使用该数据确定了 ApoE 同工型。根据 CT 暴露情况计算了人口统计学和临床变量的基线差异。使用协方差分析评估了 CT 和 ApoE 变体及其相互作用对认知功能的贡献。88 名参与者报告经历过 CT。在加性模型中,rs7412 C 等位基因可防止 CT 对运动评分产生有害影响。ApoE ε4 与 CT 的相互作用与注意力/工作记忆评分较差有关。ApoE ε4 单独存在和与 CT 结合存在与认知功能较差有关。对这种基因-环境相互作用的进一步研究可能有助于确定需要针对性干预的高危个体。

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