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首页> 外文期刊>Sleep medicine reviews >Catechol-O-methyltransferase, dopamine, and sleep-wake regulation
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Catechol-O-methyltransferase, dopamine, and sleep-wake regulation

机译：儿茶酚-O-甲基转移酶，多巴胺和睡眠觉醒调节

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Sleep and sleep disorders are complex and highly variable phenotypes regulated by many genes and environment. The catechol-O-methyltransferase (COMT) gene is an interesting candidate, being one of the major mammalian enzymes involved in the catabolism of catecholamines. The activity of COMT enzyme is genetically polymorphic due to a guanine-to-adenine transition at codon 158, resulting in a valine (Val) to methionine (Met) substitution. Individuals homozygous for the Val allele show higher COMT activity, and lower dopaminergic signaling in prefrontal cortex (PFC) than subjects homozygous for the Met allele. Since COMT has a crucial role in metabolising dopamine, it was suggested that the common functional polymorphism in the COMTgene impacts on cognitive function related to PFC, sleep-wake regulation, and potentially on sleep pathologies. The COMT Val158Met polymorphism may predict inter-individual differences in brain electroencephalography (EEG) alpha oscillations and recovery processes resulting from partial sleep loss in healthy individuals. The Val158Met polymorphism also exerts a sexual dimorphism and has a strong effect on objective daytime sleepiness in patients with narcolepsycataplexy. Since the COMT enzyme inactivates catecholamines, it was hypothesized that the response to stimulant drugs differs between COMT genotypes. Modafinil maintained executive functioning performance and vigilant attention throughout sleep deprivation in subjects with Val/Val genotype, but less in those with Met/Met genotype. Also, homozygous Met/Met patients with narcolepsy responded to lower doses of modafinil compared to Val/Val carriers. We review here the critical role of the common functional COMT gene polymorphism, COMT enzyme activity, and the prefrontal dopamine levels in the regulation of sleep and wakefulness in normal subjects, in narcolepsy and other sleep-related disorders, and its impact on the response to psychostimulants. (C) 2014 Elsevier Ltd. All rights reserved.
机译：睡眠和睡眠障碍是复杂的且易变的表型，受许多基因和环境调控。儿茶酚-O-甲基转移酶（COMT）基因是一个有趣的候选基因，是参与儿茶酚胺分解代谢的主要哺乳动物酶之一。 COMT酶的活性在遗传上是多态的，这是由于第158位密码子从鸟嘌呤到腺嘌呤的转变，导致缬氨酸（Val）取代蛋氨酸（Met）。与Met等位基因纯合的受试者相比，Val等位基因纯合的个体在前额叶皮层（PFC）中显示出更高的COMT活性和更低的多巴胺能信号传导。由于COMT在代谢多巴胺中起着至关重要的作用，因此有人提出，COMT基因中常见的功能多态性会影响与PFC，睡眠-唤醒调节相关的认知功能，并可能影响睡眠病理。 COMT Val158Met基因多态性可以预测健康个体中部分睡眠不足导致的脑电图（EEG）α振荡和恢复过程的个体差异。 Val158Met多态性还表现出性双态性，对发作性睡病患者的白天白天嗜睡产生强烈影响。由于COMT酶使儿茶酚胺失活，因此可以假设COMT基因型对刺激药物的反应不同。在具有Val / Val基因型的受试者中，莫达非尼在整个睡眠剥夺过程中保持执行功能表现并保持警惕，而在Met / Met基因型的受试者中较少。而且，与Val / Val携带者相比，患有发作性睡病的纯合的Met / Met发作性睡病患者对更低剂量的莫达非尼有反应。我们在这里回顾了正常功能COMT基因多态性，COMT酶活性和前额叶多巴胺水平在正常受试者，嗜睡症和其他与睡眠有关的疾病中对睡眠和清醒的调节中的关键作用，以及对反应的影响心理刺激剂。 （C）2014 Elsevier Ltd.保留所有权利。

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