Association of structural polymorphisms in the human
            <i>period3</i>
            gene with delayed sleep phase syndrome

Ebisawa, Takashi; Uchiyama, Makoto; Kajimura, Naofumi; Mishima, Kazuo; Kamei, Yuichi; Katoh, Masaaki; Watanabe, Takehiko; Sekimoto, Masanori; Shibui, Kayo; Kim, Keiko; Kudo, Yoshinao; Ozeki, Yuji; Sugishita, Mariko; Toyoshima, Ryoichi; Inoue, Yuichi; Yamada, Naoto; Nagase, Takahiro; Ozaki, Norio; Ohara, Osamu; Ishida, Norio; Okawa, Masako; Takahashi, Keiichi; Yamauchi, Takeshi

doi:10.1093/embo-reports/kve070

Cited by 485 publications

(325 citation statements)

References 21 publications

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“…32 In men with normal sleep patterns and those with obstructive sleep apnea, sleep fragmentation resulted in significant reductions in nocturnal testosterone; 33,34 similar disruptions in testosterone rhythm are also seen in prostate cancer patients. 35 Since variants in PER genes are associated with delayed sleep phase syndrome and extreme diurnal preference, 22,23,36,37 it is plausible that variants in PER genes are associated with different serum steroid hormone levels thus affecting risk for hormone-related cancers. Interestingly, the PER3 structural variant that was associated with an increased prostate cancer risk in a subgroup of men in this study was also linked to an increased risk for breast cancer among premenopausal women.…”

Section: Discussionmentioning

confidence: 99%

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Variants in circadian genes and prostate cancer risk: a population-based study in China

Chu

Zhu

et al. 2007

Prostate Cancer Prostatic Dis

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Circadian genes influence a variety of biological processes that are important in prostate tumorigenesis including metabolism. To determine if variants in circadian genes alter prostate cancer risk, we genotyped five variants in five circadian genes in a population-based case-control study conducted in China (187 cases and 242 controls). These variants included CRY2 rs1401417:G4C, CSNK1E rs1005473:A4C, NPAS2 rs2305160:G4A, PER1 rs2585405:G4C and PER3 54-bp repeat length variant. Men with the cryptochrome 2 (CRY2)-variant C allele had a significant 1.7-fold increased prostate cancer risk (95% confidence interval (CI), 1.1-2.7) relative to those with the GG genotype. This risk increased to 4.1-fold (95% CI, 2.2-8.0) in men who also had greater insulin resistance (IR) as compared to men with the GG genotype and less IR. In contrast, among men with less IR, the NPAS2-variant A allele was associated with decreased prostate cancer risk (odds ratio ¼ 0.5, 95% CI, 0.3-1.0) as compared to the GG genotype. Our findings, although in need of confirmation, suggest that variations in circadian genes may alter prostate cancer risk and some biological processes may modify this effect.

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Section: Discussionmentioning

confidence: 99%

“…The PER3 variant is a repeat polymorphism with four or five copies of a 54-bp repetitive sequence in exon 18 (GenBank accession no. AB047686) 22,23 and is located on chromosome 17p13.1. Details of the PCR-based sequence-length polymorphism analysis are described elsewhere.…”

Section: Biological Specimen Collection and Genetic Analysismentioning

confidence: 99%

Variants in circadian genes and prostate cancer risk: a population-based study in China

Chu

Zhu

et al. 2007

Prostate Cancer Prostatic Dis

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“…The primate-specific (Jenkins et al, 2005), variablenumber tandem-repeat (VNTR) polymorphism within the coding region of the clock gene PERIOD3 (PER3) contains a 54-nucleotide unit that is repeated 4 (PER3 4 allele) or 5 (PER3 5 allele) times in humans (Ebisawa et al, 2001). In young people, the PER3 VNTR predicts diurnal preference such that those homozygous for the long repeat (PER3 5/5 ) prefer earlier wake-up and sleep time (Archer et al, 2003;Lázár et al, in press).…”

Section: Introductionmentioning

confidence: 99%

Interindividual differences in circadian rhythmicity and sleep homeostasis in older people: effect of a PER3 polymorphism

Viola

Chellappa

Archer

et al. 2012

Neurobiology of Aging

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Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the extent of these age-related changes differs considerably between individuals. Interindividual differences in homeostatic sleep regulation in young volunteers are associated with the variable-number, tandem-repeat (VNTR) polymorphism (rs57875989) in the coding region of the circadian clock gene PERIOD3 (PER3). However, predictors of these interindividual differences have yet to be identified in older people. Sleep electroencephalographic (EEG) characteristics and circadian rhythms were assessed in 26 healthy older volunteers (55-75 years) selected on the basis of homozygosity for either the long or short allele of the PER3 polymorphism. Homozygosity for the longer allele (PER3 5/5 ) associated with a phase-advance in the circadian melatonin profile and an earlier occurrence of the melatonin peak within the sleep episode. Furthermore, older PER3 5/5 participants accumulated more nocturnal wakefulness, had increased EEG frontal delta activity (0.75-1.50 Hz), and decreased EEG frontal sigma activity (11-13 Hz) during non-rapid eye movement (REM) sleep compared with PER3 4/4 participants. Our results indicate that the polymorphism in the clock gene PER3 may contribute to interindividual differences in sleep and circadian physiology in older people.

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“…We have genotyped European SAD patients and healthy matched controls for four single nucleotide polymorphisms in genes related to intrinsic circadian oscillators; CLOCK 3111 C/T (Katzenberg et al, 1998), Period2 1244 Gly/Glu (NCBI dbSNP database (www.ncbi.nlm.nih.gov): rs934945), Period3 647 Val/Gly (Ebisawa et al, 2001), and NPAS2 471 Leu/Ser (Celera Human SNP Database (www.cds.celera. com): CV2153849).…”

Section: Introductionmentioning

confidence: 99%

“…There are studies reporting that CLOCK 3111 C/T, which is located in the 3 0 flanking region of the CLOCK gene, is associated with diurnal preference (Katzenberg et al, 1998), but not major depressive disorder (Desan et al, 2000), and Period3 647 Val/Gly is suggested to be the causative polymorphism in a Period3 haplotype associated with delayed sleep phase syndrome (Ebisawa et al, 2001). There are no published association studies for Period2 1244 Gly/Glu or NPAS2 471 Leu/Ser.…”

Section: Introductionmentioning

confidence: 99%

Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

Johansson

Willeit

Smedh

et al. 2002

Neuropsychopharmacol

310

194

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Disturbed circadian rhythms have been observed in seasonal affective disorder (SAD). The aim of this study was to further investigate this connection, and to test for potential association between polymorphisms in circadian clock-related genes and SAD, seasonality (seasonal variations in mood and behavior), or diurnal preference (morningness-eveningness tendencies). A total of 159 European SAD patients and 159 matched controls were included in the genetic analysis, and subsets were screened for seasonality (n ¼ 177) and diurnal preference (n ¼ 92). We found that diurnal preference was associated with both SAD and seasonality, supporting the hypothesis of a link between circadian rhythms and seasonal depression. The complete case-control material was genotyped for polymorphisms in the CLOCK, Period2, Period3, and NPAS2 genes. A significant difference between patients and controls was found for NPAS2 471 Leu/Ser (w 2 ¼ 9.90, Bonferroni corrected P ¼ 0.035), indicating a recessive effect of the leucine allele on disease susceptibility (w 2 ¼ 6.61, Bonferroni corrected P ¼ 0.050). Period3 647 Val/Gly was associated with self-reported morningness-eveningness scores (n ¼ 92, oneway ANOVA: F ¼ 4.99, Bonferroni corrected P ¼ 0.044), with higher scores found in individuals with at least one glycine allele (t ¼ 3.1, Bonferroni corrected P ¼ 0.013). A second, population-based sample of individuals selected for high (n ¼ 127) or low (n ¼ 98) degrees of seasonality, was also genotyped for NPAS2 471 Leu/Ser. There was no significant difference between these seasonality extreme groups, and none of the polymorphisms studied were associated with seasonality in the SAD case-control material (n ¼ 177). In conclusion, our results suggest involvement of circadian clock-related polymorphisms both in susceptibility to SAD and diurnal preference.

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Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome

Cited by 485 publications

References 21 publications

Variants in circadian genes and prostate cancer risk: a population-based study in China

Variants in circadian genes and prostate cancer risk: a population-based study in China

Interindividual differences in circadian rhythmicity and sleep homeostasis in older people: effect of a PER3 polymorphism

Circadian Clock-Related Polymorphisms in Seasonal Affective Disorder and their Relevance to Diurnal Preference

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