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Polymorphism in the PER3 Promoter Associates with Diurnal Preference and Delayed Sleep Phase Disorder

Archer, SN, Carpen, JD, Gibson, M, Lim, GH, Johnston, JD, Skene, DJ and von Schantz, M (2010) Polymorphism in the PER3 Promoter Associates with Diurnal Preference and Delayed Sleep Phase Disorder SLEEP, 33 (5). 695 - 701. ISSN 0161-8105

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Abstract

Study Objectives: To screen the PER3 promoter for polymorphisms and investigate the phenotypic associations of these polymorphisms with diurnal preference, delayed sleep phase disorder/syndrome (DSPD/DSPS), and their effects on reporter gene expression. Design: Interspecific comparison was used to define the approximate extent of the PER3 promoter as the region between the transcriptional start site and nucleotide position −874. This region was screened in DNA pools using PCR and direct sequencing, which was also used to screen DNA from individual participants. The different promoter alleles were cloned into a luciferase expression vector and a deletion library created. Promoter activation was measured by chemiluminescence. Setting: N/A Patients or Participants: DNA samples were obtained from volunteers with defined diurnal preference (3 x 80, selected from a pool of 1,590), and DSPD patients (n = 23). Interventions: N/A Measurements and Results: We verified three single nucleotide polymorphisms (G −320T, C −319A, G −294A), and found a novel variable number tandem repeat (VNTR) polymorphism (−318 1/2 VNTR). The −320T and −319A alleles occurred more frequently in DSPD compared to morning (P = 0.042 for each) or evening types (P = 0.006 and 0.033). The allele combination TA2G was more prevalent in DSPD compared to morning (P = 0.033) or evening types (P = 0.002). Luciferase expression driven by the TA2G combination was greater than for the more common GC2A (P < 0.05) and the rarer TA1G (P < 0.001) combinations. Deletion reporter constructs identified two enhancer regions (−703 to −605, and −283 to −80). Conclusions: Polymorphisms in the PER3 promoter could affect its expression, leading to potential differences in the observed functions of PER3.

Item Type: Article
Additional Information: Posted with permission from the American Academy of Sleep Medicine.
Uncontrolled Keywords: Circadian rhythms, clock genes, genetic polymorphisms, sleep disorders, FACTOR-KAPPA-B, CIRCADIAN CLOCK, LENGTH POLYMORPHISM, PERIPHERAL-TISSUES, GENE, DEPRIVATION, GENOTYPE, PERIOD3, RHYTHM, EXPRESSION
Divisions: Faculty of Health and Medical Sciences > Biochemistry and Physiology
Depositing User: Symplectic Elements
Date Deposited: 18 May 2012 09:16
Last Modified: 23 Sep 2013 19:12
URI: http://epubs.surrey.ac.uk/id/eprint/207034

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