title: A silent polymorphism in the PER1 gene associates with extreme diurnal preference in humans.
abstract: 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 PER1 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.
authors.affiliation: Centre for Chronobiology, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, GU2 7XH, UK.
authors.forename: Jayshan D
authors.initials: JD
authors.lastname: Carpen
authors.affiliation: Centre for Chronobiology, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, GU2 7XH, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: von Schantz
authors.affiliation: Department of Neurology and Sleep-Wake Disorders, Hospital de Gelderse Vallei, 6710, Ede, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Smits
authors.affiliation: Centre for Chronobiology, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, GU2 7XH, UK.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Skene
authors.affiliation: Centre for Chronobiology, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, GU2 7XH, UK. simon.archer@surrey.ac.uk.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Archer
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D018797:Cell Cycle Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D056950:Period Circadian Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012890:Sleep / Q000235:genetics; D020178:Sleep Disorders, Circadian Rhythm / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D018797:Cell Cycle Proteins; C539022:PER1 protein, human; D056950:Period Circadian Proteins