National Neurological AIDS Bank, Department of Neurology, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA, USA.
J Clin Exp Neuropsychol. 2012;34(1):78-91. doi: 10.1080/13803395.2011.623118. Epub 2011 Nov 14.
Dopaminergic dysfunction is a putative mechanism underlying HIV-associated neurocognitive disorders. Dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) have been specifically implicated. We report analyses examining the main effects of functional polymorphisms within dopamine-modulating genes, as well as their interactive effects with disease severity, upon neurocognitive functioning in HIV+ adults.
A total of 184 HIV+ adults were included in the analysis. Three polymorphisms were examined within dopamine-modulating genes: COMT val158met, BDNF val66met, and the DAT 3' variable number tandem repeat. Separate hierarchical regression analyses for five neurocognitive domains (working memory, processing speed, learning, memory, motor) were conducted. Predictor variables were age, ethnicity, gender, education, CD4+ T-cell count, current depression, genotype, and an interaction term capturing genotype and disease severity (CD4).
None of the polymorphisms or HIV disease variables significantly improved the hierarchical regression models. Younger age, higher education, and Caucasian ethnicity were almost invariably associated with better functioning across all five cognitive domains. A trend was noted for current depression as a predictor of motor and learning ability.
This study did not find evidence to support direct or interactive effects of dopamine-related genes and HIV disease severity on neurocognitive functioning.
多巴胺能功能障碍是 HIV 相关神经认知障碍的潜在机制。多巴胺转运蛋白（DAT）、脑源性神经营养因子（BDNF）和儿茶酚-O-甲基转移酶（COMT）特别涉及其中。我们报告了分析，研究了多巴胺调节基因中的功能多态性的主要效应，以及它们与疾病严重程度的相互作用，对 HIV 阳性成年人的神经认知功能的影响。
共纳入 184 名 HIV 阳性成年人进行分析。在多巴胺调节基因中检查了三个多态性：COMT val158met、BDNF val66met 和 DAT 3'可变数串联重复。对五个神经认知领域（工作记忆、加工速度、学习、记忆、运动）进行了单独的层次回归分析。预测变量为年龄、种族、性别、教育程度、CD4+ T 细胞计数、当前抑郁、基因型和捕捉基因型和疾病严重程度（CD4）的交互项。
没有一个多态性或 HIV 疾病变量显著改善了层次回归模型。在所有五个认知领域，年龄较小、受教育程度较高和白种人种族与更好的功能几乎总是相关。当前抑郁作为运动和学习能力的预测因子呈趋势。
本研究没有发现多巴胺相关基因和 HIV 疾病严重程度对神经认知功能有直接或交互影响的证据。
