PER3 polymorphism predicts sleep structure and waking performance
PER3 polymorphism predicts sleep structure and waking performance
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DOI：
10.1016/j.cub.2007.01.073
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发表时间：
2007-04-03
期刊：
影响因子：
9.2
通讯作者：
Dijk, Derk-Jan
中科院分区：
文献类型：
--
作者：
Viola, Antoine U.;Archer, Simon N.;Dijk, Derk-Jan
昼夜节律和睡眠稳态相互作用来调节睡眠-觉醒周期[1-4]，但睡眠-觉醒调节个体差异的遗传基础仍然很大程度上未知[5]。 PERIOD 基因被认为通过影响昼夜节律来导致睡眠时间的个体差异 [6]，但不影响睡眠稳态 [7, 8]。我们在一项前瞻性研究中量化了生物钟基因 PERIOD3 (PER3) [9, 10] 编码区的可变串联重复多态性对睡眠-觉醒调节的贡献，其中仅根据 PER3 基因型选择了 24 名健康参与者。较长等位基因 (PER3(5/5)) 的纯合性对睡眠结构有相当大的影响，包括睡眠稳态的几个标志物：与 PER3(4/4) 个体相比，慢波睡眠 (SWS) 和非快速眼动 (非快速眼动) 睡眠中的脑电图 (EEG) 慢波活动以及清醒和快速眼动睡眠期间的 θ 和 α 活动均高于 PER3(4/4) 个体。此外，PER3(5/5)个体因睡眠不足而导致的认知能力下降明显更大。相比之下，褪黑激素、皮质醇和外周 PER3 mRNA 表达的昼夜节律并未受到影响。数据显示，PER3 的这种多态性预测了睡眠不足引起的表现下降的个体差异，并且这种不同的易感性可能是由其对睡眠稳态的影响介导的。
Circadian rhythmicity and sleep homeostasis interact to regulate sleep-wake cycles [1-4], but the genetic basis of individual differences in sleep-wake regulation remains largely unknown [5]. PERIOD genes are thought to contribute to individual differences in sleep timing by affecting circadian rhythmicity [6], but not sleep homeostasis [7, 8]. We quantified the contribution of a variable-number tandem-repeat polymorphism in the coding region of the circadian clock gene PERIOD3 (PER3) [9, 10] to sleep-wake regulation in a prospective study, in which 24 healthy participants were selected only on the basis of their PER3 genotype. Homozygosity for the longer allele (PER3(5/5)) had a considerable effect on sleep structure, including several markers of sleep homeostasis: slow-wave sleep (SWS) and electroencephalogram (EEG) slow-wave activity in non-rapid eye movement (non-REM) sleep and theta and alpha activity during wakefulness and REM sleep were all increased in PER3(5/5) compared to PER3(4/4) individuals. In addition, the decrement of cognitive performance in response to sleep loss was significantly greater in the PER3(5/5) individuals. By contrast, the circadian rhythms of melatonin, cortisol, and peripheral PER3 mRNA expression were not affected. The data show that this polymorphism in PER3 predicts individual differences in the sleep-loss-induced decrement in performance and that this differential susceptibility may be mediated by its effects on sleep homeostasis.