A silent polymorphism in the PER1 gene associates with extreme diurnal preference in humans
A silent polymorphism in the PER1 gene associates with extreme diurnal preference in humans
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DOI：
10.1007/s10038-006-0060-y
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发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Archer, Simon N.
中科院分区：
文献类型：
--
作者：
Carpen, Jayshan D.;von Schantz, Malcolm;Archer, Simon N.
这三种PERIOD蛋白形成了控制脊椎动物生物钟周期性的分子机制的主要负反馈成分。人类PER2和PER3基因内的遗传变异与昼夜偏好和睡眠时间紊乱有关。我们筛选了PER 1的编码区，以及5 '和3'非翻译区和启动子区的多态性。外显子18的T2434C多态性，同义替换，与极端昼夜偏好相关。C等位基因在极端早晨偏好的受试者中（频率= 0.24）比极端晚上偏好的受试者（频率= 0.12）更频繁。两个等位基因与睡眠期延迟综合征之间均无显著相关性。这种多态性可能对RNA的可翻译性有直接影响，或者与另一种多态性连锁不平衡，这种多态性在DNA、RNA或蛋白质水平上影响PER 1的表达。这是第一次报道的PERI多态性和极端昼夜偏好之间的关联。在PER 1中功能重要的多态性是罕见的，这可能表明它比其他PER基因受到更严格的选择压力。
The three PERIOD proteins form a major negative feedback component of the molecular mechanism governing the periodicity of the vertebrate circadian clock. Genetic variations within the human PER2 and PER3 genes have been linked with diurnal preference and disorders of sleep timing. We screened the coding region of PER1, as well as the 5'- and 3'untranslated regions and the promoter region, for polymorphisms. The T2434C polymorphism in exon 18, a synonymous substitution, associated with extreme diurnal preference. The C allele was more frequent in subjects with extreme morning preference (frequency = 0.24) than in subjects with extreme evening preference (frequency = 0.12). No significant association was observed between either allele and delayed sleep phase syndrome. This polymorphism may have a direct effect on RNA translatability, or be in linkage disequilibrium with another polymorphism which affects PER1 expression at the DNA, RNA, or protein level. This is the first reported association between a PERI polymorphism and extreme diurnal preference. Functionally important polymorphisms in PER1 are rare, which may indicate that it is subject to more stringent selection pressure than the other PER genes.