Sundermann Erin E, Bishop Jeffrey R, Rubin Leah H, Little Deborah M, Meyer Vanessa J, Martin Eileen, Weber Kathleen, Cohen Mardge, Maki Pauline M
Department of Neurology, Albert Einstein College of Medicine, 1165 Morris Park Ave., New York, NY, 10461, USA,
J Neurovirol. 2015 Feb;21(1):81-91. doi: 10.1007/s13365-014-0305-z. Epub 2014 Dec 17.
The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p < 0.05). A significant serostatus by genotype interaction (p < 0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p < 0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected Val/Val carriers showed significantly greater prefrontal activation compared with HIV-uninfected Val/Val carriers (p < 0.01). Conversely, HIV-uninfected Met allele carriers demonstrated significantly greater prefrontal activation compared with HIV-infected Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.
儿茶酚-O-甲基转移酶基因（COMT）的Val158Met（rs4680）单核苷酸多态性（SNP）通过影响多巴胺（DA）代谢来影响执行功能和前额叶功能。人类免疫缺陷病毒（HIV）和Val158Met SNP的Val等位基因均与执行功能受损和前额叶功能低效有关。本研究采用行为学和神经影像学技术，以确定HIV血清状态与COMT基因型在女性工作记忆和前额叶功能方面的独立关联和交互作用。在行为学研究中，54名感染HIV的女性和33名未感染HIV的女性完成了言语N-back任务的0-back、1-back和2-back条件，这是一项工作记忆测试。在影像学研究中，36名女性（23名感染HIV，13名未感染HIV）在完成N-back任务时接受了功能磁共振成像（fMRI）评估。与未感染HIV的女性相比，感染HIV的女性在N-back任务中的表现明显更差（p<0.05）。基因型与血清状态的显著交互作用（p<0.01）表明，在Val/Val基因型携带者中，而非Met等位基因携带者中，感染HIV的女性在所有N-back条件下的表现均显著差于未感染HIV的对照组（p<0.01）。与行为学研究结果类似，基因型与血清状态的交互作用表明，与未感染HIV的Val/Val基因型携带者相比，感染HIV的Val/Val基因型携带者前额叶激活明显增强（p<0.01）。相反，未感染HIV的Met等位基因携带者比感染HIV的Met等位基因携带者表现出更强的前额叶激活。研究结果表明，HIV感染与Val/Val COMT基因型相结合会导致感染HIV个体出现工作记忆缺陷和前额叶功能改变。
