title: [Functional polymorphisms in clock genes and circadian rhythm sleep disorders].
abstract: Polymorphisms in clock genes induce circadian rhythm sleep disorders. Mutations in Per2 gene (S662G) or Casein Kinasel delta (CK16) gene (T44A) cause Familial advanced sleep phase syndrome. Missense polymorphisms in Per3 (V647G) and CK1e (S408N) genes increase or decrease the risk of developing delayed sleep phase syndrome. All of these polymorphisms seem to affect the phosphorylation of the clock proteins. Some of the polymorphisms in CK1, which shows reduced enzyme activity in vitro, induced increased phosphorylation of PER proteins in in vivo assays. Careful attention should be paid to analyze the complex system composed of feedback loops, such as the biological clock.
authors.affiliation: Department of Sleep Disorder Research, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan. t-ebisawa@umin.net
authors.forename: Takashi
authors.initials: T
authors.lastname: Ebisawa
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D048149:Casein Kinase 1 epsilon / Q000235:genetics; D048148:Casein Kinase Idelta / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D010766:Phosphorylation; D011110:Polymorphism, Genetic / Q000235:genetics*; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; C421902:PER2 protein, human; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D014157:Transcription Factors; D048149:Casein Kinase 1 epsilon; D048148:Casein Kinase Idelta