scholarly journals Role of Circadian Clock Genes in Sudden Cardiac Death: A Pilot Study

2017 ◽  
Vol 26 (4) ◽  
pp. 347-354 ◽  
Author(s):  
Naoto Tani ◽  
Tomoya Ikeda ◽  
Shigeki Oritani ◽  
Tomomi Michiue ◽  
Takaki Ishikawa
2007 ◽  
Vol 24 (4) ◽  
pp. 573-580 ◽  
Author(s):  
RONALD DORENBOS ◽  
MASSIMO CONTINI ◽  
HAJIME HIRASAWA ◽  
STEFANO GUSTINCICH ◽  
ELIO RAVIOLA

The mammalian neural retina contains single or multiple intrinsic circadian oscillators that can be directly entrained by light cycles. Dopaminergic amacrine (DA) cells represent an especially interesting candidate as a site of the retinal oscillator because of the crucial role of dopamine in light adaptation, and the widespread distribution of dopamine receptors in the retina. We hereby show by single-cell, end-point RT-PCR that retinal DA cells contain the transcripts for six core components of the circadian clock: Bmal1, Clock, Cry1, Cry2, Per1, and Per2. Rod photoreceptors represented a negative control, because they did not appear to contain clock transcripts. We finally confirmed that DA cells contain the protein encoded by the Bmal1 gene by comparing immunostaining of the nuclei of DA cells in the retinas of wildtype and Bmal1−/− mice. It is therefore likely that DA cells contain a circadian clock that anticipates predictable variations in retinal illumination.


2017 ◽  
Vol 42 (3) ◽  
pp. 266-273 ◽  
Author(s):  
Joanna Kotwica-Rolinska ◽  
Lenka Pivarciova ◽  
Hanka Vaneckova ◽  
David Dolezel

2010 ◽  
Vol 8 (1) ◽  
pp. 2-8
Author(s):  
Norio K ISHIDA ◽  
Daisuke UCHIDA ◽  
Ryosuke DOI ◽  
Katsutaka OISHI ◽  
Sachiko CHIKAHISA ◽  
...  

2007 ◽  
Vol 9 (3) ◽  
pp. 333-342 ◽  

The study of molecular clock mechanisms in psychiatric disorders is gaining significant interest due to data suggesting that a misalignment between the endogenous circadian system and the sleep-wake cycle might contribute to the clinical status of patients suffering from a variety of psychiatric disorders. Sleep disturbances in major depressive disorder (MDD) are characterized by increased sleep latency, poorer sleep efficiency reduced latency to the first rapid eye movement (REM) sleep episode, and early-morning awakening, but there is little data to indicate a role of circadian clock genes in MDD. There is also relatively little information regarding the role of clock genes in anxiety. In contrast, a significant amount of evidence gathered in bipolar disorder (BPD) patients suggests a circadian rhythm disorder, namely an advanced circadian rhythm and state-dependent alterations of REM sleep latency. Most research on the role of clock genes in BPD has focused on polymorphisms of CLOCK, but the lithium target GSK3 may also play a significant role. A circadian phase shift is also theorized to contribute to the pathophysiology of winter seasonal affective disorder (SAD). Certain allelic combinations of NPAS2, PER3, and BMAL1 appear to contribute to the risk of SAD. In chronic schizophrenia, disturbances of sleep including insomnia and reduced sleep efficiency have been observed. Genetic studies have found associations with CLOCK, PER1, PER3, and TIMELESS. Sleep and circadian changes associated with dementia due to Alzheimer's disease suggest a functional change in the circadian master clock, which is supported by postmortem studies of clock gene expression in the brain.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Clara Benna ◽  
Senthilkumar Rajendran ◽  
Giovanna Spiro ◽  
Chiara Menin ◽  
Luigi Dall’Olmo ◽  
...  

Abstract Background Melanoma is the deadliest of skin cancers and has an increasing annual incidence worldwide. It is a multi-factorial disease most likely arising from both genetic predisposition and environmental exposure to ultraviolet light. Genetic variability of the components of the biological circadian clock is recognized to be a risk factor for different type of cancers. Moreover, two variants of a clock gene, RORA, have been associated with melanoma patient’s prognosis. Our aim is to test the hypothesis that specific single nucleotide polymorphisms (SNPs) of the circadian clock genes may significantly influence the predisposition to develop cutaneous melanoma or the outcome of melanoma patients. Methods We genotyped 1239 subjects, 629 cases of melanoma and 610 healthy controls in 14 known SNPs of seven selected clock genes: AANAT, CLOCK, NPAS2, PER1, PER2, RORA, and TIMELESS. Genotyping was conducted by q-PCR. Multivariate logistic regression was employed for susceptibility of melanoma assessment, modeled additively. Subgroup analysis was performed by gender. For the female subgroup, a further discrimination was performed by age. For prognosis of melanoma assessment, multivariate Cox proportional hazard regression was employed. The Benjamini–Hochberg method was utilized as adjustment for multiple comparisons. Results We identified two RORA SNPs statistically significant with respect to the association with melanoma susceptibility. Considering the putative role of RORA as a nuclear steroid hormone receptor, we conducted a subgroup analysis by gender. Interestingly, the RORA rs339972 C allele was associated with a decreased predisposition to develop melanoma only in the female subgroup (OR 0.67; 95% CI 0.51–0.88; P = 0.003) while RORA rs10519097 T allele was associated with a decreased predisposition to develop melanoma only in the male subgroup (OR 0.62; 95% CI 0.44–0.87; P = 0.005). Moreover, the RORA rs339972 C allele had a decreased susceptibility to develop melanoma only in females aged over 50 years old (OR 0.67; 95% CI 0.54–0.83; P = 0.0002). None of the studied SNPs were significantly associated with the prognosis. Conclusions Overall, we cannot ascertain that circadian pathway genetic variation is involved in melanoma susceptibility or prognosis. Nevertheless, we identified an interesting relationship between melanoma susceptibility and RORA polymorphisms acting in sex-specific manner and which is worth further future investigation.


Author(s):  
Junyu Zhai ◽  
Shang Li ◽  
Jingwen Hu ◽  
Minzhi Gao ◽  
Yun Sun ◽  
...  

Abstract Context Previous work has demonstrated the role of the circadian clock in ovarian steroid hormone synthesis and attributed embryo implantation failure associated with arrhythmic circadian clock genes to insufficient ovarian-derived progesterone synthesis. Research on expression of core circadian clock genes in the endometrium itself and possible roles in compromised endometrial receptivity and recurrent implantation failure (RIF) are limited. Objective We aimed to assess the core circadian clock gene profiling in human endometrium across the menstrual cycle and the possible gene interaction networks in the endometrial receptivity of window of implantation (WOI) as well as RIF. Methods The study was initially an in silico study, with confirmatory lab-based data from primary human endometrial stromal cells (hESCs) as well as endometrial biopsies obtained from 60 women undergoing gynecological surgery in a clinical research center. The study included 30 RIF women and 30 age-matched and body mass index–matched controls. Results Initial data mining and bioinformatics analysis of human endometrial microarray datasets across the menstrual cycle and between RIF women versus controls demonstrated the varied expression of core circadian clock genes across menstrual cycle, including the key role of PER2 in WOI and RIF. A PER2-centered network was investigated in the regulation of endometrial receptivity. We also confirmed the evidently increased mRNA expression of SHTN1, RXFP1, KLF5, and STEAP4 in the endometrium of RIF women, displaying the same trend as PER2 did, without any changes in MT1E and FKBP5. Treatment of PER2 siRNA in hESCs verified the positive regulation of PER2 to SHTN1, KLF5, and STEAP4. Conclusion Aberrant expression of endometrial PER2 might contribute to impaired endometrial receptivity and development of RIF via regulating SHTN1, KLF5, and STEAP4.


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