客观睡眠表型与神经肽S受体基因功能多态性的遗传关联。
Genetic association of objective sleep phenotypes with a functional polymorphism in the neuropeptide S receptor gene.
作者信息
Spada Janek, Sander Christian, Burkhardt Ralph, Häntzsch Madlen, Mergl Roland, Scholz Markus, Hegerl Ulrich, Hensch Tilman
机构信息
LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Department of Psychiatry and Psychotherapy, Universität Leipzig, Leipzig, Germany.
LIFE - Leipzig Research Center for Civilization Diseases, Universität Leipzig, Leipzig, Germany; Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
出版信息
PLoS One. 2014 Jun 4;9(6):e98789. doi: 10.1371/journal.pone.0098789. eCollection 2014.
BACKGROUND
The neuropeptide S receptor (NPSR1) and its ligand neuropeptide S (NPS) have received increased attention in the last few years, as both establish a previously unknown system of neuromodulation. Animal research studies have suggested that NPS may be involved in arousal/wakefulness and may also have a crucial role in sleep regulation. The single nucleotide polymorphism (SNP) rs324981 in NPSR1 has begun to shed light on a function of the NPS-system in human sleep regulation. Due to an amino acid exchange, the T-allele leads to an increased sensitivity of the NPSR1. In the only genome-wide association study to date on circadian sleep parameters in humans, an association was found between rs324981 and regular bedtime. However, the sleep parameters in this study were only measured by self-rating. Therefore, our study aimed to replicate these findings using an objective measure of sleep.
METHODS
The study included n = 393 white subjects (62-79 years) who participated in an actigraphic assessment for determining sleep duration, rest duration, sleep onset, rest onset and sleep onset latency. Genotyping of the SNP rs324981 was performed using the TaqMan OpenArray System.
RESULTS
The genotype at rs324981 was not significantly associated with rest onset (bedtime) or sleep onset (p = .146 and p = .199, respectively). However, the SNP showed a significant effect on sleep- and rest duration (p = .007 and p = .003, respectively). Subjects that were homozygous for the minor T-allele had a significantly decreased sleep- and rest duration compared to A-allele carriers.
CONCLUSION
The results of this study indicate that the sleep pattern in humans is influenced by the NPS-system. However, the previously reported association between bedtime and rs324981 could not be confirmed. The current finding of decreased sleep duration in T/T allele carriers is in accordance with studies in rodents reporting similar results after NPS application.
背景
神经肽S受体（NPSR1）及其配体神经肽S（NPS）在过去几年中受到了越来越多的关注，因为它们共同建立了一个此前未知的神经调节系统。动物研究表明，NPS可能参与觉醒/清醒过程，并且在睡眠调节中可能也起着关键作用。NPSR1中的单核苷酸多态性（SNP）rs324981已开始揭示NPS系统在人类睡眠调节中的功能。由于氨基酸交换，T等位基因导致NPSR1的敏感性增加。在迄今为止唯一一项关于人类昼夜睡眠参数的全基因组关联研究中，发现rs324981与规律就寝时间之间存在关联。然而，该研究中的睡眠参数仅通过自我评定来测量。因此，我们的研究旨在使用客观的睡眠测量方法来重复这些发现。
方法
该研究纳入了n = 393名白人受试者（62 - 79岁），他们参与了一项活动记录仪评估，以确定睡眠时间、休息时间、入睡时间、休息开始时间和入睡潜伏期。使用TaqMan OpenArray系统对SNP rs324981进行基因分型。
结果
rs324981的基因型与休息开始时间（就寝时间）或入睡时间均无显著关联（分别为p = 0.146和p = 0.199）。然而，该SNP对睡眠时间和休息时间有显著影响（分别为p = 0.007和p = 0.003）。与A等位基因携带者相比，携带次要T等位基因纯合子的受试者睡眠时间和休息时间显著减少。
结论
本研究结果表明，人类的睡眠模式受NPS系统影响。然而，先前报道的就寝时间与rs324981之间的关联未能得到证实。目前关于T/T等位基因携带者睡眠时间减少的发现与啮齿动物研究结果一致，这些研究报道了应用NPS后出现类似结果。
Zotero 插件