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Circadian Genes (circadian + gene)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Ala394Thr polymorphism in the clock gene NPAS2: A circadian modifier for the risk of non-Hodgkin's lymphoma

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2007
Yong Zhu
Abstract Circadian disruption is theorized to cause immune dysregulation, which is the only established risk factor for non-Hodgkin's lymphoma (NHL). Genes responsible for circadian rhythm are also involved in cancer-related biological pathways as potential tumor suppressors. However, no previous studies have examined associations between circadian genes and NHL risk. In this population-based case control study (n = 455 cases; 527 controls), we examined the only identified nonsynonymous polymorphism (Ala394Thr; rs2305160) in the largest circadian gene, neuronal PAS domain protein 2 (NPAS2), in order to examine its impact on NHL risk. Our results demonstrate a robust association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with reduced risk of NHL (OR = 0.66, 95% CI: 0.51,0.85, p = 0.001), especially B-cell lymphoma (OR = 0.61, 95% CI: 0.47,0.80, p ,, 0.0001). These findings provide the first molecular epidemiologic evidence supporting a role of circadian genes in lymphomagenesis, which suggests that genetic variations in circadian genes might be a novel panel of promising biomarkers for NHL and warrants further investigation. © 2006 Wiley-Liss, Inc. [source]

Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2002
Caroline Kopp
Abstract A limited set of genes, Clock, Bmal1, mPer1, mPer2, mCry1 and mCry2, has been shown to be essential for the generation of circadian rhythms in mammals. It has been recently suggested that circadian genes might be involved in sleep regulation. We investigated the role of mPer1 and mPer2 genes in the homeostatic regulation of sleep by comparing sleep of mice lacking mPER1 (mPer1 mutants) or a functional mPER2 (mPer2 mutants), and wild-type controls (WT) after 6 h of sleep deprivation (SD). Our main result showed that after SD, all mice displayed the typical increase of slow-wave activity (SWA; EEG power density between 0.75 and 4 Hz) in nonREM sleep, reflecting the homeostatic response to SD. This increase was more prominent over the frontal cortex as compared to the occipital cortex. The genotypes did not differ in the effect of SD on the occipital EEG, while the effect on the frontal EEG was initially diminished in both mPer mutants. Differences between the genotypes were seen in the 24-h distribution of sleep, reflecting especially the phase advance of motor activity onset observed in mPer2 mutants. While the daily distribution of sleep was modulated by mPer1 and mPer2 genes, sleep homeostasis reflected by the SWA increase after 6-h SD was preserved in the mPer mutants. The results provide further evidence for the independence of the circadian and the homeostatic components underlying sleep regulation. [source]

Opposing actions of neuropeptide Y and light on the expression of circadian clock genes in the mouse suprachiasmatic nuclei

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2002
Elizabeth S. Maywood
Abstract The circadian clockwork of the hypothalamic suprachiasmatic nuclei (SCN) is synchronized by light and by nonphotic cues. The core timing mechanism is cell-autonomous, based on an autoregulatory transcriptional/translational feedback loop of circadian genes and their products. This study investigated the effects of neuropeptide Y (NPY), a potent nonphotic resetting cue, and its interaction with light in regulating clock gene expression in the SCN in vivo. Injection of NPY adjacent to the SCN and transfer to darkness 7 h before scheduled lights out, shifted the circadian activity,rest cycle. Exposure to light for 1 h immediately after NPY infusion blocked this behavioural response. NPY-induced shifts were accompanied by suppression of both mPer1 and mPer2 mRNA in the SCN, assessed 3 h after infusion. mPer mRNAs were not altered 1 h after infusion. Levels of mClock mRNA or mCLOCK immunoreactivity in the SCN were not affected by NPY at either time point. In parallel to the behavioural response, the NPY-induced suppression of mPer genes in the SCN was attenuated when a light pulse was delivered immediately after the infusion. These results identify mPer1 and mPer2 as molecular targets for both photic and nonphotic (NPY-induced) resetting of the clockwork, and support a synthetic model of circadian entrainment based upon convergent up- and downregulation of mPer expression. [source]

Ala394Thr polymorphism in the clock gene NPAS2: A circadian modifier for the risk of non-Hodgkin's lymphoma

Disturbance of circadian gene expression in hepatocellular carcinoma

MOLECULAR CARCINOGENESIS, Issue 12 2008
Yueh-Min Lin
Abstract Circadian rhythm plays an important role in the regulation of digestive system. The human circadian rhythm is controlled by at least nine circadian genes. The aims of this study are to understand the expression of the circadian genes between hepatocellular carcinoma tissues and nontumor tissues, and to explore the possible mechanism(s) contributing to the difference. We analyzed differential expression of the 9 circadian genes in 46 hepatocellular carcinoma and paired noncancerous tissues by real-time quantitative RT-PCR and immunohistochemical detection. We also tested the possible regulatory mechanism(s) by direct sequencing and methylation PCR analysis. Our results showed that decreased expression levels of PER1, PER2, PER3, CRY2, and TIM in hepatocellular carcinomas were observed. Decreased-expression of these genes was not caused by genetic mutations, but by several factors, such as promoter methylation, overexpression of EZH2 or other factors. The downexpression of more circadian genes may result in disturbance of cell cycle, and it is correlated with the tumor size. Downregulation of circadian genes results in disturbance of circadian rhythm in hepatocellular carcinoma which may disrupt the control of the central pacemaker and benefit selective survival of cancerous cells and promote carcinogenesis. © 2008 Wiley-Liss, Inc. [source]

Promoter methylation in circadian genes of endometrial cancers detected by methylation-specific PCR

MOLECULAR CARCINOGENESIS, Issue 10 2006
Mu-Chin Shih
Abstract Methylation of CpG dinucleotides in the promoter sequence of a gene can lead to deregulated and suppressed gene expression. In this study, we have developed procedures for methylation-specific polymerase chain reaction (MSP) and sequencing analysis to determine CpG methylation status of the promoter sequences of nine circadian genes in 35 endometrial cancers (EC) and paired noncancerous endometrial tissues. DNA methylation was found in the promoter sequences of PER1, PER2, and CRY1, but not of other six circadian genes in the ECs and normal tissues examined. Eleven of the 35 EC tissues showed CpG methylation in the promoter sequences of PER1, PER2, or CRY1. Of these 11 cases, 1 had promoter methylation in all the three genes, 1 in PER1 and PER2, 3 in PER1 and CRY1, and 6 in PER1, respectively. In comparison, promoter CpG methylation of PER1, PER2, or CRY1 was found in only 7 of 35 paired noncancerous tissues including 2 in PER1 and PER2, 2 in PER1, and 3 in CRY1. In summary, promoter methylation in the PER1, PER2, or CRY1 circadian genes was detected in about one-third of EC and one-fifth of noncancerous endometrial tissues of 35 paired specimens indicating possible disruption of the circadian clock in the development of EC. © 2006 Wiley-Liss, Inc. [source]