Roomaney Aqeedah Abbas, Womersley Jacqueline Samantha, Swart Patricia Cathryn, Spies Georgina, Seedat Soraya, Hemmings Sian Megan Joanna
Division of Molecular and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
South African Medical Research Council / Stellenbosch University Genomics of Brain Disorders Research Unit, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town, South Africa.
IBRO Neurosci Rep. 2021 Dec 8;12:45-54. doi: 10.1016/j.ibneur.2021.12.003. eCollection 2022 Jun.
HIV/AIDS is a major public health burden in South Africa, currently affecting an estimated 13.5% of the population. Despite improved access to antiretroviral therapies, HIV-associated neurocognitive disorders (HAND), characterised by a spectrum of neurocognitive impairment, emotional disturbances and motor abnormalities, continue to persist. Gene-environment interactions contribute to HAND pathophysiology and previous research has identified childhood trauma as an environmental risk factor. Dopaminergic signalling in the prefrontal cortex plays a key role in cognitive function. Thus, variants in genes encoding the dopamine transporter (DAT) and catechol-O-methyltransferase (COMT), which are responsible for dopamine transport and metabolism, could represent genetic risk factors for HAND. This study investigated whether the variable number of tandem repeats (VNTR) and Val158Met (rs4680) polymorphisms are associated with longitudinal change in cognitive function in the context of childhood trauma and HIV. Participants ( = 49 HIV-negative and = 64 HIV-positive women) completed the Childhood Trauma Questionnaire - Short Form (CTQ-SF) and provided blood for genetic analyses. Global cognitive scores were generated from baseline and one-year follow-up assessments. Following polymerase chain reaction, genotypes were determined using gel electrophoresis and confirmed by Sanger sequencing. Baseline global cognitive scores, genotype, HIV status and CTQ-SF scores were regressed on one-year global cognitive scores in regression models. Analysis of variance was used to examine the effect of including predictor variable interactions on model fit. HIV seropositivity was associated with poorer cognitive performance at one-year follow-up ( = 2.46 ×10). The combination of HIV and 10-repeat homozygosity ( 10/10) was associated with reduced global cognitive scores in longitudinal models ( = 0.010). Including the interaction between 10/10, childhood trauma, and HIV explained significantly more of the variance in longitudinal cognitive scores ( = 0.008). There were no significant associations with the genotype. Our research indicates that childhood trauma and genetic variation in contribute toward the aetiology of HAND. Future studies in larger cohorts are warranted to verify these results.
艾滋病毒/艾滋病是南非主要的公共卫生负担，目前估计影响着13.5%的人口。尽管抗逆转录病毒疗法的可及性有所改善，但以一系列神经认知障碍、情绪障碍和运动异常为特征的与艾滋病毒相关的神经认知障碍（HAND）仍然存在。基因-环境相互作用促成了HAND的病理生理学，先前的研究已将童年创伤确定为一种环境风险因素。前额叶皮质中的多巴胺能信号在认知功能中起关键作用。因此，编码多巴胺转运体（DAT）和儿茶酚-O-甲基转移酶（COMT）的基因变异，它们负责多巴胺的转运和代谢，可能代表HAND的遗传风险因素。本研究调查了串联重复序列可变数目（VNTR）和Val158Met（rs4680）多态性是否与童年创伤和艾滋病毒背景下认知功能的纵向变化相关。参与者（49名艾滋病毒阴性和64名艾滋病毒阳性女性）完成了儿童创伤问卷简表（CTQ-SF）并提供血液用于基因分析。全球认知分数由基线和一年随访评估得出。经过聚合酶链反应后，使用凝胶电泳确定基因型，并通过桑格测序进行确认。在回归模型中，将基线全球认知分数、基因型、艾滋病毒状态和CTQ-SF分数对一年全球认知分数进行回归分析。方差分析用于检验纳入预测变量相互作用对模型拟合的影响。在一年随访时，艾滋病毒血清阳性与较差的认知表现相关（P = 2.46×10）。在纵向模型中，艾滋病毒与10重复纯合子（10/10）的组合与全球认知分数降低相关（P = 0.010）。纳入10/10、童年创伤和艾滋病毒之间的相互作用显著解释了纵向认知分数中更多的方差（P = 0.008）。与Val158Met基因型无显著关联。我们的研究表明，童年创伤和DAT基因变异促成了HAND的病因。有必要在更大的队列中进行未来研究以验证这些结果。
