<i>Per3</i> length polymorphism in patients with type 2 diabetes mellitus

Ramanujam, Karthikeyan; Marimuthu, G.; Sooriyakumar, Murugesan; BaHammam, Ahmed S.; Spence, D. Warren; Pandi-Perumal, Seithikurippu R.; Brown, Gregory M.; Cardinali, Daniel P.

doi:10.1515/hmbci-2013-0049

Cited by 19 publications

(17 citation statements)

References 36 publications

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“…These effects appear to be independent of sleep loss or diminished sleep quality, suggesting that disruption of the timing system alone can lead to metabolic dysfunction [19,20]. In support of this notion, the probability of a genetic polymorphism in the PER3 genetic locus was greater among individuals with type 2 diabetes, suggesting that altered activity of the PER3 protein, and thus the molecular clock, may be an independent risk factor for metabolic disease [93]. Finally, data show that the amount of social jet lag (a delay in mid-sleep time on 'off days' relative to work days) experienced is positively correlated with elevated BMI, independent of nightly sleep duration [94].…”

Section: Sleep Disturbance Circadian Disruption and Altered Glucose mentioning

confidence: 86%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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In mammals, the circadian timing system drives rhythms of physiology and behaviour, including the daily rhythms of feeding and activity. The timing system coordinates temporal variation in the biochemical landscape with changes in nutrient intake in order to optimise energy balance and maintain metabolic homeostasis. Circadian disruption (e.g. as a result of shift work or jet lag) can disturb this continuity and increase the risk of cardiometabolic disease. Obesity and metabolic disease can also disturb the timing and amplitude of the clock in multiple organ systems, further exacerbating disease progression. As our understanding of the synergy between the timing system and metabolism has grown, an interest has emerged in the development of novel clock-targeting pharmaceuticals or nutraceuticals for the treatment of metabolic dysfunction. Recently, the pineal hormone melatonin has received some attention as a potential chronotherapeutic drug for metabolic disease. Melatonin is well known for its sleep-promoting effects and putative activity as a chronobiotic drug, stimulating coordination of biochemical oscillations through targeting the internal timing system. Melatonin affects the insulin secretory activity of the pancreatic beta cell, hepatic glucose metabolism and insulin sensitivity. Individuals with type 2 diabetes mellitus have lower night-time serum melatonin levels and increased risk of comorbid sleep disturbances compared with healthy individuals. Further, reduced melatonin levels, and mutations and/or genetic polymorphisms of the melatonin receptors are associated with an increased risk of developing type 2 diabetes. Herein we review our understanding of molecular clock control of glucose homeostasis, detail the influence of circadian disruption on glucose metabolism in critical peripheral tissues, explore the contribution of melatonin signalling to the aetiology of type 2 diabetes, and discuss the pros and cons of melatonin chronopharmacotherapy in disease management.

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Section: Sleep Disturbance Circadian Disruption and Altered Glucose mentioning

confidence: 86%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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“…Similar relations are observed for Bmal2 polymorphism rs7958822 in obese men and women (OR 2.2 and 2.7, resp.) [ 56 ] and the deletion/insertion of 54 base pair sequences of five repeat alleles on Per3 gene ( rs57875989 ) [ 57 , 58 ]. In contrast, the Per2 polymorphism rs7602358 is associated with a protection from type 2 diabetes in the UK population, which suggests that not all polymorphisms are negative for health [ 53 ].…”

Section: Clock Genes and Metabolic Disordermentioning

confidence: 99%

Evidences of Polymorphism Associated with Circadian System and Risk of Pathologies: A Review of the Literature

Valenzuela

Vera

Venegas

et al. 2016

International Journal of Endocrinology

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The circadian system is a supraphysiological system that modulates different biological functions such as metabolism, sleep-wake, cellular proliferation, and body temperature. Different chronodisruptors have been identified, such as shift work, feeding time, long days, and stress. The environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer, preeclampsia, diabetes, and mood disorder. This system is organized by transcriptional/tranductional feedback loops of clock genes Clock, Bmal1, Per1–3, and Cry1-2. How molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown. This research describes different genetic variations in the population and how these are associated with risk of cancer, metabolic diseases such as diabetes, obesity, and dyslipidemias, and also mood disorders such as depression, bipolar disease, excessive alcohol intake, and infertility. Finally, these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined.

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“…We have shown that a primate-specific, variable number, tandem repeat (VNTR), coding region polymorphism in human PER3 is associated with diurnal preference, delayed sleep phase disorder, sleep homeostasis, increased body mass index (BMI) in people who sleep late during work days, cognitive performance, fMRI-assessed brain activity, lower intelligence in people with long sleep duration during work days, and cardiac regulation (Archer et al, 2003;Viola et al, 2007Viola et al, , 2012Groeger et al, 2008;Vandewalle et al, 2009Vandewalle et al, , 2011Lazar et al, 2012;Lo et al, 2012). Others have reported associations with bipolar disorder (Benedetti et al, 2008), schizophrenia (Karthikeyan et al, 2014a), white matter integrity (Bollettini et al, 2017), type 2 diabetes (Karthikeyan et al, 2014b), cancer (Alexander et al, 2015), light sensitivity (Chellappa et al, 2012), hormone secretion (Wirth et al, 2013), cytokine secretion (Guess et al, 2009), and addiction (Zou et al, 2008). In addition, we have also shown that transgenically humanizing mouse Per3 with the VNTR polymorphism phenocopies some aspects of human sleep homeostasis such as increased theta power during wake and delta power during sleep (Hasan et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

A Topological Cluster of Differentially Regulated Genes in Mice Lacking PER3

Veen

Laing

Bae

et al. 2020

Front. Mol. Neurosci.

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Polymorphisms in the human circadian clock gene PERIOD3 (PER3) are associated with a wide variety of phenotypes such as diurnal preference, delayed sleep phase disorder, sleep homeostasis, cognitive performance, bipolar disorder, type 2 diabetes, cardiac regulation, cancer, light sensitivity, hormone and cytokine secretion, and addiction. However, the molecular mechanisms underlying these phenotypic associations remain unknown. Per3 knockout mice (Per3 −/−) have phenotypes related to activity, sleep homeostasis, anhedonia, metabolism, and behavioral responses to light. Using a protocol that induces behavioral differences in response to light in wild type and Per3 −/− mice, we compared genome-wide expression in the eye and hypothalamus in the two genotypes. Differentially expressed transcripts were related to inflammation, taste, olfactory and melatonin receptors, lipid metabolism, cell cycle, ubiquitination, and hormones, as well as receptors and channels related to sleep regulation. Differentially expressed transcripts in both tissues co-localized with Per3 on an ∼8Mbp region of distal chromosome 4. The most down-regulated transcript is Prdm16, which is involved in adipocyte differentiation and may mediate altered body mass accumulation in Per3 −/− mice. eQTL analysis with BXD mouse strains showed that the expression of some of these transcripts and also others co-localized at distal chromosome 4, is correlated with brain tissue expression levels of Per3 with a highly significant linkage to genetic variation in that region. These data identify a cluster of transcripts on mouse distal chromosome 4 that are co-regulated with Per3 and whose expression levels correlate with those of Per3. This locus lies within a topologically associating domain island that contains many genes with functional links to several of the diverse non-circadian phenotypes associated with polymorphisms in human PER3.

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Per3 length polymorphism in patients with type 2 diabetes mellitus

Cited by 19 publications

References 36 publications

Chronomedicine and type 2 diabetes: shining some light on melatonin

Chronomedicine and type 2 diabetes: shining some light on melatonin

Evidences of Polymorphism Associated with Circadian System and Risk of Pathologies: A Review of the Literature

A Topological Cluster of Differentially Regulated Genes in Mice Lacking PER3

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