Circadian Rhythm Genes Research Articles

Relationship between circadian rhythm-related genes and extracellular matrix: implications for sleep deprivation

BackgroundSleep deprivation (SD) can lead to the development of various pathological disorders. The extracellular matrix (ECM) compositions and circadian rhythm genes are two pivotal variables of SD. However, their relationships remain undefined during SD.MethodsA mouse SD model was established using a modified multiplatform water environment method. The expression of nerve growth factor (NGF) in mouse hippocampus was detected by an immunofluorescence (IF) method. Protein expression was assessed by western blot, and mRNA analysis was performed by quantitative real-time PCR (qRT-PCR). The differentially expressed genes after SD, the genes associated with stromal score, and gene expression correlation were analyzed by bioinformatic analysis.ResultsThe mouse model of SD was successfully established, as evidenced by the changed morphology, increased Bax and NGF levels, and downregulated Bcl-2 in mouse hippocampus after SD. The differentially expressed genes after SD were closely associated with the ECM compositions. The ECM composition metalloproteinase 9 (MMP9) was under-expressed in mouse hippocampus after SD. The hippocampal MMP9 expression was correlated with the expression levels of circadian genes PER2, PER3, TIMELESS, FBXL3, and NFIL3. PER2 and TIMELESS were upregulated in mouse hippocampus after SD.ConclusionThe current findings suggest a correlation between ECM composition MMP9 and circadian rhythm-related genes PER2 and TIMELESS in mouse hippocampus after SD, providing a novel understanding of the disorders after SD.

Signatures of adaptation in myopia-related genes on the sunlight exposure hypothesis

BackgroundMyopia is a common eye disorder that results from gene-environment interactions. The prevalence of myopia varies across populations, and exposure to bright sunlight may prevent its development. We hypothesize that local adaptation to light environments during human migration played a role in shaping the genetic basis of myopia, and we aim to investigate how the environment influences the genetic basis of myopia.MethodWe utilized the whole-genome variant data of the 1000 Genomes Project for analysis. We searched myopia-associated loci that were under selection in Europeans using population branch statistics and the number of segregating sites by length statistics. The outliers of these statistics were enriched in the Kyoto Encyclopedia of Genes and Genomes pathways and the gene ontology biological process terms in searching for pathways that were under selection. We applied Bayesian inference to estimate the correlation between environmental factors and allele frequencies of the selected loci and performed causal inference of myopia using two-sample Mendelian randomization analysis.ResultsWe detected signatures of adaptation in vision and light perception pathways, supporting our hypothesis of sunlight adaptation. We discovered a strong correlation between latitude and allele frequencies in genes that are under significant selection, and we found pleiotropic effects of pigmentation or circadian rhythm genes on myopia, indicating that sunlight exposure influences the genetic diversity of myopia.ConclusionsMyopia genes involved in light perception showed signs of selection. Local adaptation during human migration shaped the genetic basis of myopia and may have influenced its global prevalence distribution.

Antioxidant and Geroprotective Properties of the Extract of Mountain Ash (<i>Sorbus aucuparia</i> L.) Fruits

Plant polyphenols are characterized by a wide range of biological activities, including antioxidant properties, and have a high geroprotective potential. The purpose of this work was to investigate the effect of the extract of rowan berries (Sorbus aucuparia L.) on the lifespan and stress resistance of Drosophila melanogaster with the identification of possible mechanisms of its biological activity. It has been established that the ethanol extract of S. aucuparia berries, the main components of which are rutin and cyanidin-3-rutinoside, has a pronounced antioxidant activity in vitro. At the same time, treatment with rowan berry extract increased the r-esistance of D. melanogaster males to starvation, but reduced resistance to hyperthermia. In females, the e-xtract reduced resistance to oxidative stress but increased resistance to hyperthermia. The effects of rowan berry extract on longevity depended both on its concentration and on the sex of fruit flies. In response to treatment with rowan berry extract, D. melanogaster males and females showed slight differences in the background level of expression of cellular stress response genes, including heat shock genes (hsp27, hsp68, hsp83), oxidative stress resistance genes (hif1, nrf2, sod1), circadian rhythm genes (clk, per), and the longevity gene sirt1, which may explain the differences in the observed effects.

First Evidence for the Daily Oscillation of Circadian Rhythm Gene, BMAL1, in Human Villous Trophoblast Cells

First Evidence for the Daily Oscillation of Circadian Rhythm Gene, BMAL1, in Human Villous Trophoblast Cells

Identification of key circadian rhythm genes in skin aging based on bioinformatics and machine learning.

Skin aging is often accompanied by disruption of circadian rhythm and abnormal expression of circadian rhythm-related genes. In this study, we downloaded skin aging expression datasets from the GEO database and utilized bioinformatics and machine learning methods to explore circadian rhythm genes and pathways involved in skin aging, revealing the pathological and molecular mechanisms of skin aging. Results showed that 39 circadian rhythm-related genes (CRGs) were identified in skin aging, and these CRGs were enriched in signaling pathways such as glucagon signaling pathway, insulin resistance, thyroid hormone signaling pathway, and adipocytokine signaling pathway. Three key skin aging-related CRGs, SIRT1, ARNTL, and ATF4, were identified based on machine learning. Additionally, we found that skin aging was associated with infiltration of immune cells including NK cells activated, Macrophages M1, Mast cells resting, T cells CD4 memory activated, and Macrophages M2, and the expression of the three key skin aging-related CRGs was correlated with these immune cells. Finally, SIRT1, ARNTL, and ATF4 were all down-regulated in skin aging and had a good ability to distinguish young skin tissue from aging skin tissue. In conclusion, three key CRGs, including SIRT1, ARNTL, and ATF4, which are closely related to skin aging, were obtained based on bioinformatics and machine learning technology screening. These three key CRGs were potential risk genes for skin aging and also associated with changes in the immune microenvironment in skin aging. The language used in this paragraph follows the guidelines for scientific writing specified by SCI, making it clear and concise.

Silencing the rhythm gene AgCLK-1 reduced feeding of Aphis gossypii

The cotton aphid Aphis gossypii Glover is an important cotton pest, and means of controlling this insect is a primary research focus. Although biological rhythm is an important mechanism that regulates numerous insect processes and activities, its role in cotton aphid has not been elucidated. In the present study, four highly-expressed circadian rhythm genes were selected from the cotton aphid genome database and their physicochemical properties and protein structures were analyzed. These genes were in the Takeout, Timeless, and Timeless interacting-related families, and the corresponding proteins contained highly-conserved Swis and TIMELESS domains. Gene expression analysis at multiple developmental stages revealed differing expression patterns between the four genes. AgCLK-1 had the highest relative expression of the four, especially during the nymph period. Silencing AgCLK-1 caused a significant refusal of the cotton aphids to feed at 1, 3, and 5 d of treatment. These results demonstrated that AgCLK-1 played a key role in regulating the feeding behavior of cotton aphid. This new functional understanding provides novel insights into cotton aphid biology and suggests new targeting strategies for agricultural pest control.

The genome of the deep-sea anemone Actinernus sp. contains a mega-array of ANTP-class homeobox genes.

Members of the phylum Cnidaria include sea anemones, corals and jellyfish, and have successfully colonized both marine and freshwater habitats throughout the world. The understanding of how cnidarians adapt to extreme environments such as the dark, high-pressure deep-sea habitat has been hindered by the lack of genomic information. Here, we report the first chromosome-level deep-sea cnidarian genome, of the anemone Actinernus sp., which was 1.39 Gbp in length and contained 44 970 gene models including 14 806 tRNA genes and 30 164 protein-coding genes. Analyses of homeobox genes revealed the longest chromosome hosts a mega-array of Hox cluster, HoxL, NK cluster and NKL homeobox genes; until now, such an array has only been hypothesized to have existed in ancient ancestral genomes. In addition to this striking arrangement of homeobox genes, analyses of microRNAs revealed cnidarian-specific complements that are distinctive for nested clades of these animals, presumably reflecting the progressive evolution of the gene regulatory networks in which they are embedded. Also, compared with other sea anemones, circadian rhythm genes were lost in Actinernus sp., which likely reflects adaptation to living in the dark. This high-quality genome of a deep-sea cnidarian thus reveals some of the likely molecular adaptations of this ecologically important group of metazoans to the extreme deep-sea environment. It also deepens our understanding of the evolution of genome content and organization of animals in general and cnidarians in particular, specifically from the viewpoint of key developmental control genes like the homeobox-encoding genes, where we find an array of genes that until now has only been hypothesized to have existed in the ancient ancestor that pre-dated both the cnidarians and bilaterians.

The modulatory effect of oolong tea polyphenols on intestinal flora and hypothalamus gene expression in a circadian rhythm disturbance mouse model

The interaction between host circadian rhythm and gut microbes through the gut-brain axis provides new clues for tea polyphenols to improve host health. Our present research showed that oolong tea polyphenols (OTP) improved the structural disorder of the intestinal flora caused by continuous darkness, thereby modulating the production of metabolites related to pyruvate metabolism, glycolysis/gluconeogenesis, and tryptophan metabolism to alleviate the steady-state imbalance. After fecal microbiota transplantation from the OTP group, the single-cell transcriptomic analysis revealed that OTP significantly increased the number of hypothalamus cell clusters, up-regulated the number of astrocytes and fibroblasts, and enhanced the expression of circadian rhythm genes Cry2, Per3, Bhlhe41, Nr1d1, Nr1d2, Dbp and Rorb in hypothalamic cells. Our results confirmed that OTP can actively improve the intestinal environmental state as well as internal/peripheral circadian rhythm disorders and cognitive impairment, with potential prebiotic functional characteristics to notably contribute to host health.

The Relationship between Clock Genes, Sirtuin 1, and Mitochondrial Activity in Head and Neck Squamous Cell Cancer: Effects of Melatonin Treatment.

The circadian clock is a regulatory system, with a periodicity of approximately 24 h, which generates rhythmic changes in many physiological processes, including mitochondrial activity. Increasing evidence links chronodisruption with aberrant functionality in clock gene expression, resulting in multiple diseases such as cancer. Melatonin, whose production and secretion oscillates according to the light-dark cycle, is the principal regulator of clock gene expression. In addition, the oncostatic effects of melatonin correlate with an increase in mitochondrial activity. However, the direct links between circadian clock gene expression, mitochondrial activity, and the antiproliferative effects of melatonin in cancers, including head and neck squamous cell carcinoma (HNSCC), remain largely unknown. In this study, we analyzed the effects of melatonin on HNSCC cell lines (Cal-27 and SCC9), which were treated with 500 and 1000 µM melatonin. We found that the antiproliferative effect of melatonin is not mediated by the Bmal1 clock gene. Additionally, high doses of melatonin were observed to result in resynchronization of oscillatory circadian rhythm genes (Per2 and Sirt1). Surprisingly, the resynchronizing effect of melatonin on Per2 and Sirt1 did not produce alterations in the oscillation of mitochondrial respiratory activity. These results increase our understanding of the possible antiproliferative mechanisms in melatonin in the treatment of head and neck squamous cell carcinoma and suggest that its antiproliferative effects are independent of clock genes but are directly related to mitochondrial activity.

Bioinformatics Integrative Analysis of Circadian Rhythms Effects on Atopic Dermatitis and Dendritic Cells.

Atopic dermatitis (AD) is an allergic inflammatory skin disease caused by aberrant and over-reactive immune response. Although circadian rhythm disruption is implicated in multiple immunoinflammatory conditions, including AD, the mechanisms at the molecular level underlying AD and circadian rhythms remain elusive. Bulk and single-cell RNA-sequencing data of AD patients were acquired from the Gene Expression Omnibus, including GSE121212, GSE120721, and GSE153760 datasets. A single-sample gene set enrichment analysis was performed to estimate circadian rhythm gene expression levels. A differential expression analysis was utilized to identify the key candidate genes in AD. CIBERSORT was used to quantify the proportions of immune cells, and the R package "Seurat" was utilized to investigate single-cell RNA-sequencing data. Circadian rhythm gene expression levels were lower in AD skin samples than in normal skin samples. Dendritic cells were significantly upregulated and negatively correlated with circadian rhythm gene expression levels in AD patients. Compared with circadian rhythm-related genes in the control samples, ARNTL2, NOCT, and RORC were differentially expressed in AD; ARNTL2 and NOCT were significantly upregulated, whereas RORC was significantly downregulated in AD. ARNTL2, NOCT, and RORC also showed robust abilities to diagnose AD. We validated that the abundance of the dendritic cell was positively correlated with the ARNTL2 and NOCT expression levels using bulk RNA-sequencing data of the GSE121212 and single-cell RNA-sequencing data of the GSE153760. Moreover, the functional enrichment analysis showed that the IL-17 and NF-κB signaling pathways, Th1 and Th2 cell differentiations, and primary immunodeficiency, were enriched in AD patients. The findings of this study suggested that the circadian rhythm is involved in the progression of AD, and RNTL2, NOCT, and RORC as well as dendritic cells are differentially expressed in AD. These findings could be used to introduce diagnostic and chronotherapeutic modalities for AD.

The genetics and chronobiology of cluster headache.

Cluster headache displays uniquely rhythmic patterns in its attack manifestation. This strong chronobiological influence suggests that part of the pathophysiology of cluster headache is distinctly different from migraine and has prompted genetic investigations probing these systems. This is a narrative overview of the cluster headache chronobiological phenotype from the point of view of genetics covering existing knowledge, highlighting the specific challenges in cluster headache and suggesting novel research approaches to overcome these. The chronobiological features of cluster headache are a hallmark of the disorder and while discrepancies between study results do exist, the main findings are highly reproducible across populations and time. Particular findings in subgroups indicate that the heritability of the disorder is linked to chronobiological systems. Meanwhile, genetic markers of circadian rhythm genes have been implicated in cluster headache, but with conflicting results. However, in two recently published genome wide association studies two of the identified four loci include genes with an involvement in circadian rhythm, MER proto-oncogene, tyrosine kinase and four and a half LIM domains 5. These findings strengthen the involvement of circadian rhythm in cluster headache pathophysiology. Studying chronobiology and genetics in cluster headache presents challenges unique to the disorder. Researchers are overcoming these challenges by pooling various data from different cohorts and performing meta-analyses providing novel insights into a classically enigmatic disorder. Further progress can likely be made by combining deep pheno- and genotyping.

Isorhynchophylline improves lipid metabolism disorder by mediating a circadian rhythm gene Bmal1 in spontaneously hypertensive rat.

Hypertension is a progressive metabolic disease characterized by circadian regulation of lipid metabolism disorder. Identifying specific lipid components and maintaining circadian homeostasis of lipid metabolism might be a promising therapeutic strategy for hypertension. Isorhynchophylline (IRP) can regulate lipid metabolism; however, the underlying mechanism of IRP in improving lipid metabolism rhythm disorder is still unclear. The lipid circadian biomarkers and abnormal metabolic pathways intervened by IRP were investigated using diurnal lipidomic research methods. The 24-h circadian changes in mRNA and protein expression levels of circadian genes, including Bmal1, Clock, Cry1, Cry2, Per1, and Per2, and lipid metabolism-related factors (PPARα and LPL) were determined using RT-PCR and western blot analyses, respectively. The underlying mechanisms were intensively investigated by inhibiting Bmal1. Molecular docking and drug affinity responsive target stability analyses were performed to assess the binding affinity of IRP and Bmal1. IRP treatment could effectively improve 24-h blood pressure, ameliorate the lipid metabolic rhythm disorder, reverse the expression levels of circadian rhythm genes, and regulate lipid metabolism-related genes (PPARα and LPL) by mediating Bmal1. This study highlighted the potential effects of IRP in maintaining the circadian homeostasis of lipid metabolism and the treatment of hypertension.

Circadian rhythm disturbances involved in ozone-induced glucose metabolism disorder in mouse liver

Ozone (O3) is a key environmental factor for developing diabetes. Nevertheless, the underlying mechanisms remain unclear. This study aimed to investigate alterations of glycometabolism in mice after O3 exposure and the role of circadian rhythms in this process. C57BL/6 male mice were randomly assigned to O3 (0.5 ppm) or filtered air for four weeks (4 h/day). Then, hepatic tissues of mice were collected at 4 h intervals within 24 h after O3 exposure to test. The results showed that hepatic circadian rhythm genes oscillated abnormally, mainly at zeitgeber time (ZT)8 and ZT20 after O3 exposure. Furthermore, detection of glycometabolism (metabolites, enzymes, and genes) revealed that O3 caused change in the daily oscillations of glycometabolism. The serum glucose content decreased at ZT4 and ZT20, while hepatic glucose enhanced at ZT16 and ZT24(0). Both G6pc and Pck1, which are associated with hepatic gluconeogenesis, significantly increased at ZT20. O3 exposure disrupted glycometabolism by increasing gluconeogenesis and decreasing glycolysis in mice liver. Finally, correlation analysis showed that the association between Bmal1 and O3-induced disruption of glycometabolism was the strongest. The findings emphasized the interaction between adverse outcomes of circadian rhythms and glycometabolism following O3 exposure.

Circadian Rhythm Gene CLOCK Polymorphisms and the Risk of Schizophrenia Among Iranian Patients

Background: Schizophrenia is a type of neuropsychiatric disorder that is defined by hallucinations, disturbed thinking, and cognitive impairment. However, the pathogenesis and cause of schizophrenia remain elusive. Previous research demonstrated that schizophrenic patients have irregular circadian rhythms. Circadian locomotor output cycles kaput (CLOCK) is a key component of the circadian clock system and is involved in a wide range of mammals’ physiological, metabolic, and behavioral processes. A change in the CLOCK gene may be linked to both common mental and circadian disorders. Objectives: This study aimed to investigate the possible relationship between rs1801260 and rs6811520 polymorphisms in the CLOCK gene, as the principal regulator of the circadian rhythm, with susceptibility to schizophrenia in the Iranian population. Methods: DNA samples were obtained from the venous blood of 103 people with schizophrenia and 100 unrelated healthy people in Dezful, southwest Iran. The high-resolution melting (HRM) method was used for genotyping the CLOCK gene SNPs, including rs1801260 and rs6811520. The PCR and DNA sequencing confirmed the HRM results. Results: We found a correlation between schizophrenia and the CLOCK SNP rs6811520. In addition, our findings demonstrated that the SNP rs1801260 did not contribute to schizophrenia. Conclusions: The findings of this study demonstrate that changes in the CLOCK gene may contribute to schizophrenia.

Evaluation of a circadian rhythm gene (PER3) VNTR variant in Turkish athletes

Objective Circadian rhythmicity has been shown to contribute to the regulation of key physiological and cognitive processes related to performance. The period homolog 3 (PER3) is expressed in a circadian pattern in the suprachiasmatic nucleus. Therefore, in this study, we aimed to evaluate the role of the variable tandem repeat (VNTR) variant of the PER3 gene in athletic performance in the Turkish population. Methods This study included 223 subjects, which consisted of 123 athletes and 100 sedentary controls. Blood samples were drawn from all subjects. DNA was extracted from whole-blood samples. The PER3 VNTR variant was genotyped using the polymerase chain reaction-restriction method (PCR). The results of the analyses were evaluated for statistical significance. Results The mean ages of athletes and controls were 22 ± 2.814 and 23 ± 3.561, respectively. Endurance athletes in the group were 21.1%, and sprint athletes were 78.9%. There was no statistical significance in terms of PER3 VNTR genotype distribution or allele frequency. In the recessive model, a statistically significant association was observed when the athletes were compared with the controls according to 4/4 + 4/5 versus 5/5 genotype (p = 0.020). Conclusion In this case-control study, for the first time in our country, we obtained findings suggesting that the PER3 VNTR variant may affect sports performance in the Turkish population. Results need to be replicated in different ethnic and larger samples.

Circadian gene variation in relation to breeding season and latitude in allochronic populations of two pelagic seabird species complexes

Annual cues in the environment result in physiological changes that allow organisms to time reproduction during periods of optimal resource availability. Understanding how circadian rhythm genes sense these environmental cues and stimulate the appropriate physiological changes in response is important for determining the adaptability of species, especially in the advent of changing climate. A first step involves characterizing the environmental correlates of natural variation in these genes. Band-rumped and Leach’s storm-petrels (Hydrobates spp.) are pelagic seabirds that breed across a wide range of latitudes. Importantly, some populations have undergone allochronic divergence, in which sympatric populations use the same breeding sites at different times of year. We investigated the relationship between variation in key functional regions of four genes that play an integral role in the cellular clock mechanism—Clock, Bmal1, Cry2 and Per2—with both breeding season and absolute latitude in these two species complexes. We discovered that allele frequencies in two genes, Clock and Bmal1, differed between seasonal populations in one archipelago, and also correlated with absolute latitude of breeding colonies. These results indicate that variation in these circadian rhythm genes may be involved in allochronic speciation, as well as adaptation to photoperiod at breeding locations.

Abstract P1064: Gene Editing Technologies To Understand Knockout And Over Expression Of Circadian Rhythm Regulatory Genes In Human Derived Spheroid Model.

Introduction: Human induced pluripotent stem cells (hiPSCs) have the ability to produce a huge variety of terminally differentiated cell types that can be used for tissue engineering, drug research, and cell therapy. Using CRISPR/Cas9 gene-editing technologies, hiPSCs with knockout mutations for Per1, Per2, CIITA, B2M, N-Cadherin, Connexin43 and over expression of Connexin43 were created. Cardiomyocytes (CM) were created from hiPSCs, and spheroid culture was carried out as previously described. The molecular basis of circadian regulation of human induced pluripotent stem cells (hiPSCs) is still under investigation. Methods: From hiPSC CMs, we created and described a 3D spheroid culture. We assessed the effectiveness of spheroid transplantation for cardiac healing in immunecompromised mice and pigs. We investigated border zone macrophage markers, border zone vascular density, and cell proliferation in myocardial infarction after spheroid transplantation. We used pedigree analysis and 20 years of family health diagnostics data to analyze the clinical consequences of type 2 diabetes medications among metformin combo patients in big extended family (N=30).. Results: TNF-Alpha, IL1-beta, NOS2, and IL-6 relative expression were shown to be lower in the KO group than in the WT group. Significant engraftment of hiPSC-derived cardiac spheroids was seen up to 4 weeks after transplantation, according to histological examination. Arrhythmogenicity is significantly altered by the spheroid therapy. Ventricular tachycardia may be related to macrophage immunological regulation. To further understand, we looked at the effects of a medication combination of dapagliflozin and metformin in a large extended family, where 5 out of 30 members had type 2 diabetes. One patient experienced mildly tachycardic heart issues over the course of a 20-year medication treatment. Conclusion: Our study established the promising therapeutic potential of spheroids model from hiPSC differentiated CMs to understand Circadian rhythm gene regulation.

Bipolar Disorder, Circadian Rhythm and Clock Genes.

Sleep disturbance and abnormal circadian rhythm might be closely related to bipolar disorder. Several studies involving disturbed sleep/wake cycle, changes in rhythms such as melatonin and cortisol, clock genes, and circadian preference have shown the relationship between bipolar disorder and circadian rhythm. The results differed across different studies. In some studies, a delay in the circadian rhythm was observed in the depressive episode and advanced circadian rhythm was observed during the manic episode. In other studies, a delay in circadian rhythm was observed independent of mood episodes. Accordingly, circadian rhythm disorder was proposed as a trait marker for bipolar disorder. The altered circadian rhythm may represent a pathological mechanism that contributes to the mood episodes. However, a prospective cohort study is needed for further clarification.

The role of circadian clock in the Polycystic Ovary Syndrome

The Polycystic Ovary Syndrome (PCOS) is a worldwide disease related to infertility. This intrinsic syndrome affects 5-15% of females under 18-44 age globally. There is still no exact explanation to the cause of PCOS on molecular and genetic level. PCOS has been proved to have a strong genetic predisposition. One of the symptoms of PCOS is the sleep disturbances related to circadian disorder. A numerous research has already been done on relationship between the genetic pathway and other factors in PCOS. Androgen can act as a modulator exert to effect on the receptors in SCN to change circadian rhythms. CYP17A1, one of the most important gene in the aetiology of PCOS, has also been shown as a direct CLOCK-BMAL1 target in peripheral blood mononuclear cells (PBMCs). The circadian rhythm and clock genes have already been taken in account to be related with PCOS. The circadian disorder often synergize with the loss of metabolic disorder, the steroidogenesis, to intensify the compromised fertility. This review introduces the physiological links between circadian clocks and Polycystic Ovary Syndrome. It highlights the present current researches on the molecular level associations between the circadian disorders and PCOS, which introduce a potential cause of it.

Association of the circadian rhythm gene <i>ARNTL/BMAL1</i> with personal anxiety among people aged 25–64 (WHO international program “MONICA-psychosocial (MOPSY)”)

Objective: to study associations between personal anxiety (PA) and single nucleotide polymorphism rs2278749 of the ARNTL gene among individuals aged 25–64 years living in Novosibirsk.Material and methods. Under the WHO program “MONICA-psychosocial (MOPSY)”, a random representative sample of the population aged 25–64 years in Novosibirsk was studied (725 men, mean age – 43.4±0.4 years, response – 71.3%; 710 women, mean age – 44.8±0.4 years, response – 72%). The general examination was carried out according to standard methods included in the protocol of the WHO program. To assess PA, a form of Spielberger self-assessment scales was proposed. Every second respondent underwent genotyping of the studied polymorphisms of the ARNTL gene.Results. The C/C genotype of the ARNTL gene was found in the general population in 60.7% of individuals (in 61.2% of men and 60.5% of women); the C/T genotype was found in 34.1% of individuals (in 35.1% of men and 33.5% of women) and the T/T genotype in the general population was found in 5.2% of individuals (in 3.7% of men and 6% women). The probability of PA development among carriers of the CT+TT genotypes of the ARNTL gene was 2 times higher (p<0.05) in the general population and 2.4 times (p<0.05) among women; among T allele carriers, it was 1.8 times higher (p<0.05) in the population and 2.1 times (p<0.05) among women. Carriers of the C/T genotype of the ARNTL gene were 30.3% more likely to believe that they almost always take everything too personally (p=0.024). Carriers of the C/T genotype (21%) almost always, and carriers of the T/T genotype (27.8%) often would like to be as happy as others (p=0.031). The answer “I often feel satisfaction” prevailed (38.2%) among the carriers of the C/C genotype, and the answer “Almost never feel satisfaction” among the carriers of the C/T genotype (5.9%) of the ARNTL gene (p=0.044) .Conclusion. It was found that the C/C genotype of the ARNTL gene was the most common in the population; the probability of PA occurrence among carriers of CT+TT genotypes, carriers of the T allele is 2 times higher than in carriers of other genotypes of the ARNTL gene.