Viola Antoine U, Archer Simon N, James Lynette M, Groeger John A, Lo June C Y, Skene Debra J, von Schantz Malcolm, Dijk Derk-Jan
Surrey Sleep Research Centre, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, UK.
Curr Biol. 2007 Apr 3;17(7):613-8. doi: 10.1016/j.cub.2007.01.073. Epub 2007 Mar 8.
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.
昼夜节律性与睡眠稳态相互作用以调节睡眠 - 觉醒周期[1 - 4]，但睡眠 - 觉醒调节中个体差异的遗传基础仍 largely unknown[5]。周期基因被认为通过影响昼夜节律性[6]而非睡眠稳态[7, 8]来导致睡眠时间的个体差异。我们在一项前瞻性研究中量化了昼夜节律钟基因周期3（PER3）[9, 10]编码区可变数目串联重复多态性对睡眠 - 觉醒调节的贡献，在该研究中仅根据其PER3基因型选择了24名健康参与者。较长等位基因的纯合性（PER3(5/5)）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，PER3(5/5)个体的慢波睡眠（SWS）、非快速眼动（非REM）睡眠中的脑电图（EEG）慢波活动以及清醒和REM睡眠期间的θ波和α波活动均增加。此外，PER3(5/5)个体对睡眠剥夺的认知表现下降明显更大。相比之下，褪黑素、皮质醇和外周PER3 mRNA表达的昼夜节律不受影响。数据表明，PER3中的这种多态性预测了睡眠剥夺引起的表现下降中的个体差异，并且这种易感性差异可能由其对睡眠稳态的影响介导。
