Association of job stress, FK506 binding protein 51 (FKBP5) gene polymorphisms and their interaction with sleep disturbance.

Background: Sleep disturbance is an outcome of multiple factors including environmental and genetic influences. Job stress, a complex environmental factor, likely affects sleep quality, significantly reducing the quality of life of workers. Additionally, FK506 binding protein 51 (FKBP5) may be a pathogenic factor for sleep disturbance as it regulates hypothalamic-pituitary-adrenal (HPA) axis activity, where HPA axis has been found to be involved in the regulation mechanism of sleep and stress response. Objectives: The main aim of this study was to investigate the association between job stress and FKBP5 gene polymorphism as well as their interaction with sleep disturbance in Chinese workers; to date, these relationships have not been explored. Methods: This is a cross-sectional study. A total of 675 railway workers (53.8% male) completed a short Effort-Reward Imbalance questionnaire and the Pittsburgh Sleep Quality Index. The SNaPshot single nucleotide polymorphism (SNP) assay was carried out by screening for FKBP5 SNPs in every participant. Generalized multifactor dimensionality reduction (GMDR) was used to identify the strongest G×E interaction combination. Results: The findings showed that job stress was significantly associated with sleep disturbance; specifically, scores on the PSQI subscales (sleep disturbance, sleep medication, and daytime dysfunction) exhibited significant differences between the two job stress groups (X2 = 18.10, p = 0.01). Additionally, the FKBP5 SNP rs1360780-TT (adjusted odds ratio [AOR] = 4.98, 95% confidence interval [CI] = 2.80-8.84) and rs3800373-CC genotype (AOR = 2.06, CI = 1.10-3.86) were associated with an increased risk of sleep disturbance. Job stress and rs1360780 and rs3800373 variants showed a high-dimensional interaction with sleep disturbance as determined by the GMDR model. Conclusion: The FKBP5 gene may increase susceptibility to job stress and result in sleep disturbance, especially in the presence of negative work-related events. These findings contribute to the field of sleep disturbance prevention and treatment.

Gene-environment interaction between circadian clock gene polymorphisms and job stress on the risk of sleep disturbances.

RATIONALE: Sleep disturbances was associated with numerous adverse health outcomes. Many studies have reported that long-term exposure to job stress can lead to sleep disturbances, which may be influenced by genetic and environmental factors. OBJECTIVES: This cross-sectional study investigated whether circadian clock gene polymorphisms modulated the influence of job stress on sleep disturbances in a Chinese Han population, which to our best knowledge has not been explored. METHODS: The Effort-Reward Imbalance (ERI) scale and the Pittsburgh Sleep Quality Index (PSQI) were both used to access job stress and sleep disturbances. The SNaPshot SNP assay was carried out by screening for circadian clock gene polymorphisms in every participant. Interactions associated with sleep disturbances were assessed by linear hierarchical regression analysis and SPSS macros (PROCESS). RESULTS: Linear hierarchical regression analysis showed that job stress was significantly related to sleep disturbances. Likewise, our study found a significant effect of PER2 rs2304672 polymorphisms on sleep disturbances (p < 0.01), after controlling for confounding factors. In addition, the PER2 rs2304672 genotype modulated the relationship between job stress and sleep disturbances (ß = 0.414, p = 0.007). Interestingly, further analysis of the results of the PER2 gene rs2304672 × job stress interaction showed that rs2304672 G-allele carriers had a high-risk effect on sleep disturbances under high job stress. CONCLUSIONS: Our results suggest that the PER2 rs2304672 polymorphism may modulate the influence of job stress on sleep disturbances. These findings contribute to the field of sleep disturbances prevention and treatment.

Effects of Work Stress and Period3 Gene Polymorphism and Their Interaction on Sleep Quality of Non-Manual Workers in Xinjiang, China: A Cross-Sectional Study.

Work stress has been found to be associated with sleep quality in various occupational groups, and genetic factors such as variable number tandem repeat polymorphism in the Period3 (Per3) gene also influence the circadian sleep-wake process. Therefore, the present study aimed to evaluate the sleep quality status of non-manual workers in Xinjiang, China and to analyse the effects of work stress and Per3 gene polymorphism and their interaction on sleep quality. A cluster sampling method was used to randomly select 1700 non-manual workers in Urumqi, Xinjiang. The work stress and sleep quality of these workers were evaluated using the Effort−Reward Imbalance Inventory (ERI) and the Pittsburgh Sleep Quality Index (PSQI). Next, 20% of the questionnaire respondents were randomly selected for genetic polymorphism analysis. The polymerase chain reaction-restriction fragment length polymorphism technique was used to determine Per3 gene polymorphism. The detection rate of sleep quality problems differed between the different work stress groups (p < 0.05), suggesting that non-manual workers with high levels of work stress are more likely to have sleep quality problems. Regression analysis revealed that the Per3 gene (OR = 3.315, 95% CI: 1.672−6.574) was the influencing factor for poor sleep quality after adjusting for confounding factors, such as occupation, length of service, education, and monthly income. Interaction analysis showed that Per34/5,5/5 × high work stress (OR = 2.511, 95% CI: 1.635−3.855) had a higher risk of developing sleep quality problems as compared to Per34/4 × low work stress after adjusting for confounding factors. The structural equation modelling showed no mediating effect between work stress and Per3 gene polymorphism. The results of this study show that both work stress and Per3 gene polymorphism independently affect sleep quality of nonmanual workers from Xinjiang, and the interaction between these two factors may increase the risk of sleep quality problems. Therefore, to improve sleep quality, individuals with genetic susceptibility should avoid or reduce as much as possible self-stimulation by work-related exposures such as high levels of external work stress.

Work-related stress and well-being in association with epigenetic age acceleration: A Northern Finland Birth Cohort 1966 Study.

Recent evidence indicates consistent association of low socioeconomic status with epigenetic age acceleration, measured from DNA methylation. As work characteristics and job stressors are crucial components of socioeconomic status, we investigated their association with various measures of epigenetic age acceleration. The study population included employed and unemployed men and women (n=604) from the Northern Finland Birth Cohort 1966. We investigated the association of job strain, effort-reward imbalance and work characteristics with five biomarkers of epigenetic aging (Hannum, Horvath, PhenoAge, GrimAge, and DunedinPoAm). Our results indicate few significant associations between work stress indicators and epigenetic age acceleration, limited to a range of ±2 years, and smoking recording the highest effect on GrimAge age acceleration biomarker between current and no smokers (median difference 4.73 years (IQR 1.18, 8.41). PhenoAgeAA was associated with job strain active work (ß=-1.301 95%CI -2.391, -0.212), slowing aging of less than 1.5 years, and working as white-collar slowed aging six months (GrimAgeAA ß=-0.683, 95%CI -1.264, -0.102) when compared to blue collars. Association was found for working for more than 40 hours per week that increased the aging over 1.5 years, (HorvathAA ß =2.058 95%CI 0.517,3.599, HannumAA ß=1.567, 95%CI 0.415,2.719). The pattern of associations was different between women and men and some of the estimated effects are inconsistent with current literature. Our results provide the first evidence of association of work conditions with epigenetic aging biomarkers. However, further epidemiological research is needed to fully understand how work-related stress affects epigenetic age acceleration in men and women in different societies.

hsa_circ_0111707 Is Associated With Risk of Stress-Related Type 2 Diabetes via Sponging miR-144-3p.

Introduction: Chronic stress plays an important role in the development of type 2 diabetes (T2D). Circular RNAs (circRNAs) play significant roles in regulating the pathogenesis of diseases by regulating gene expression. The aim of the present study was to identify the association between hsa_circ_0111707 and stress-related T2D. Methods: The present study was performed based on a three-part design. The association between hsa_circ_0111707 in peripheral blood mononuclear cells (PBMCs) and T2D and stress-related variables were assessed in a cross-sectional study. The causal relationship of hsa_circ_0111707 on T2D was further investigated in a nested case-control study. miR-144-3p as the miRNA target of hsa_circ_0111707 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results: The relative expression of hsa_circ_0111707 was significantly lower in the T2D and impaired fasting glucose (IFG) cases in comparison with controls. The hsa_circ_0111707 expression was significantly negatively correlated with miR-144-3p expression and plasma cortisol concentration and positively correlated with NR3C1 expression. In addition, hsa_circ_0111707 expression was negatively correlated with scores of "demands at work" and "insecurity at work" of Copenhagen Psychosocial Questionnaire (COPSOQ). Decreased hsa_circ_0111707 expression was associated with increased risk of T2D development. Functional analysis demonstrated that hsa_circ_0111707 functions as a sponge for miR-144-3p. Conclusion: hsa_circ_0111707 is associated with risk of T2D development via sponging miR-144-3p. hsa_circ_0111707 in PBMCs can be considered a potential biomarker of stress-related T2D.

Effects of Occupational Stress and Circadian CLOCK Gene Polymorphism on Sleep Quality of Oil Workers in Xinjiang, China.

BACKGROUND This study investigated the effect of occupational stress and circadian clock gene polymorphism on sleep disorder of oil workers in Xinjiang, China. MATERIAL AND METHODS We enrolled 2300 Xinjiang oil workers who had been working for at least 1 year. The Chinese revised version of the Occupational Stress Questionnaire (OSI-R), the Pittsburgh Sleep Quality Index (PSQI), and General Survey Questionnaire were used. A total of 308 subjects were selected for stress hormone measurements and gene polymorphism analysis of the circadian clock genes CLOCK, PER2, and PER3. RESULTS The occupational stress scores were influenced by sex, smoking, marital status, age, and work type. Different work shift groups and different professional title groups had statistically significant sleep disorder incidences (P<0.05). The middle and high occupational stress groups had significantly higher subjective sleep quality, total PSQI scores, daytime dysfunction factor scores, and sleep disorder than in the low occupational stress group (P<0.05). CLOCK gene rs1801260 locus carrying TC genotype (OR=0.412, 95% CI=0.245-0.695), and CLOCK gene rs6850524 locus carrying GC and CC genotypes decreased sleep disorder risk (OR1=0.357, 95% CI1=0.245-0.695; OR2=0.317, 95% CI2=0.128-0.785). The main factors affecting the sleep quality of oil workers were length of service, individual strain capacity, glucocorticoid levels, Per3 gene, and the rs6850524 loci of CLOCK gene. CONCLUSIONS Occupational stress has an adverse effect on the sleep quality of workers. CLOCK gene and Per3 gene may increase risk of sleep disorders.

Oxytocin receptor gene polymorphisms moderate the relationship between job stress and general trust in Chinese Han university teachers.

BACKGROUND: Chronic exposure to stressful work environments can influence general trust. High job stress is associated with low trust in others. Both environmental and genetic factors contribute to general trust; however, few empirical studies have explored the important role of gene-environment interactions on general trust. In this study, the moderating roles of the polymorphisms OXTR rs53576 and OXTR rs2268490 in the relationship between job stress and general trust were evaluated. METHODS: 362 healthy Chinese Han university teachers (196 males, 165 females, and 1 undisclosed) were included (Mage = 39.80, SD = 9.16). Standardized questionnaires about demographic characteristics, job stress, and general trust scale were collected. Blood samples were collected for OXTR rs53576 and rs2268490 genotyping. RESULTS: Job stress scores showed a significant negative main effect on general trust (p < 0.001), while OXTR rs53576 and rs2268490 did not (p > 0.05). The effect of the interaction between job stress and OXTR rs53576 or rs2268490 on general trust was significant, even after controlling for gender and age. High job stress was associated with low general trust in OXTR rs53576 homozygous individuals (GG/AA) or OXTR rs2268490 CT individuals, demonstrating that the GA genotype in OXTR rs53576 and CC/TT genotype in OXTR rs2268490 are protective genotype of general trust. LIMITATIONS: This study used a cross-sectional design, only considered Chinese Han university teachers, and only examined two polymorphisms in OXTR. CONCLUSIONS: Our findings provide evidence that gene-environment interactions influence general trust and identify a new locus (rs2268490) underlying this phenotype.

Cross-Sectional Survey of Mental Health Risk Factors and Comparison of the Monoamine oxidase A Gene DNA Methylation Level in Different Mental Health Conditions among Oilfield Workers in Xinjiang, China.

The incidence of psychological problems among occupational groups is becoming increasingly more serious, and adverse psychological conditions will seriously affect the working ability of occupational groups and harm the health of their bodies. This study adopted a multi-stage stratified cluster sampling method to conduct a cross-sectional survey on the mental health of 3631 oil workers in Karamay, Xinjiang from March 2017 to June 2018. The mental health status of oil workers was evaluated using the Symptom Checklist-90, and mental health risk factors were evaluated. The correlation between the monoamine oxidase A (MAOA) gene and mental health was analyzed, and the DNA methylation level of the MAOA gene was compared between the normal group and the abnormal group. The results show the incidence of mental health problems among oil workers according to differences in age, nationality, type of work, length of service, professional title, shift work, and marital status. The evaluation of mental health risk factors revealed that shift work, occupational stress, and high payment/low return affect mental health. The somatization scores of different genotypes of rs6323 in the MAOA gene were statistically significant (p < 0.05), suggesting that the somatization scores of different genotypes of rs6323 were different. According to the average rank, the TT genotype group had the highest score, followed by the GT genotype group, and the GG genotype group had the lowest score. The level of DNA methylation in the abnormal group was lower than that in the normal group (p < 0.05). The results suggested that occupational mental health can be enhanced by improving shift work, reducing stress, and balancing effort and reward. This preliminary investigation suggests that methylation status can affect mental health, indicating that methylation level may be a predictor of mental health status.

Work-Related Stress, Physio-Pathological Mechanisms, and the Influence of Environmental Genetic Factors.

Work-related stress is a growing health problem in modern society. The stress response is characterized by numerous neurochemicals, neuroendocrine and immune modifications that involve various neurological systems and circuits, and regulation of the gene expression of the different receptors. In this regard, a lot of research has focused the attention on the role played by the environment in influencing gene expression, which in turn can control the stress response. In particular, genetic factors can moderate the sensitivities of specific types of neural cells or circuits mediating the imprinting of the environment on different biological systems. In this current review, we wish to analyze systematic reviews and recent experimental research on the physio-pathological mechanisms that underline stress-related responses. In particular, we analyze the relationship between genetic and epigenetic factors in the stress response.

Interactive effects of corticotropin-releasing hormone receptor 1 gene and work stress on burnout in medical professionals in a Chinese Han population.

BACKGROUND: Burnout is a worked-related stress syndrome caused by long-term exposure to a stressful environment. Dysregulation of the hypothalamic- pituitary- adrenal (HPA) axis may be involved in both stress and burnout; an evaluation of genetic polymorphisms which alter activity in the HPA may be predictive of how likely an environment is to produce burnout. METHODS: Using a cross-sectional design, this study examined whether corticotrophin-releasing hormone receptor 1 (CRHR1) gene polymorphism rs110402 is a risk factor for burnout; further, it explores whether the interaction of stress × CRHR1 gene predicts burnout in the healthcare workers in a Chinese Han population. House and Rizzo's work stress scale, Sources of Pressure Scale and Maslach Burnout Inventory-General Survey were administered to 712 participants from a large general hospital in Beijing. The CRHR1 rs110402 polymorphism was genotyped in 376 participants. RESULTS: Our results showed significant positive inter-correlations between stressor, work stress and depressive scores (all p < 0.001) with only one exception. Males, younger age and higher educational level were associated with burnout (all p < 0.05). The presence of the CRHR1 rs110402 genotype was not correlated with the presence of job stress or burnout. However, we found statistically significant interaction between CRHR1 rs110402 and job stress on burnout (p < 0.05). Individuals homozygous for the A allele reported significantly higher emotional exhaustion than G allele carriers in the high stress group. LIMITATIONS: The sample was only chosen from the medical professions, and the sample size was relatively small. Only one polymorphism in CRHR1 gene was analyzed, while only about half of the total individuals were genotyped. CONCLUSIONS: Our results suggest a close relationship between work-related stress and burnout and that the A allele of the CRHR1 rs110402 polymorphism may enhance feelings of emotional exhaustion when experiencing work-related stress.

Association of glucocorticoid receptor gene polymorphism and occupational stress with hypertension in desert petroleum workers in Xinjiang, China.

BACKGROUND: The aim of this study was to investigate the occupational stress and hypertension in desert petroleum workers in Xinjiang, and to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension. METHODS: Using cluster sampling, 1280 desert petroleum workers of 3 petroleum fields in Xinjiang Karamay were randomly selected as the target group for this study. According to the inclusion criteria, a total of 1080 workers were included as the baseline for this study. We followed these workers for 2 years to investigate their occupational stress and hypertension. The polymorphism of GR gene was detected by polymerase chain reaction-restriction fragment length polymorphism. We applied appropriate statistical methods to analyze the association of occupational stress and glucocorticoid receptor (GR) gene polymorphism with the presence of hypertension. RESULTS: After 2 years of follow-up, there were 995 desert petroleum workers in the queue. The study showed that the incidence of hypertension in desert petroleum workers were 19.4%. Compared with the baseline data, the level of occupational stress increased, and with the increase of occupational stress, the incidence of hypertension was gradually increasing. A positive relationship was observed in the GR BCL1 gene polymorphisms and hypertension. Relative to the CC genotype, carries of the GG genotype had a significantly higher risk of hypertension (OR = 2.830). With the combination of genotype CG and GG, carries of CG and GG increased the risk of hypertension (adjusted OR = 2.238, 95%CI:1.104-4.940). There was no significant association between GR G678S gene polymorphisms and hypertension. CONCLUSION: GR gene polymorphism and occupational stress of desert petroleum workers were important risk factors for hypertension.

Relationship between Job Stress and 5-HT2A Receptor Polymorphisms on Self-Reported Sleep Quality in Physicians in Urumqi (Xinjiang, China): A Cross-Sectional Study.

The serotonin receptor (5-HTR) plays a key role in sleep quality regulation. Job-related stress is an important factor that influences sleep quality. However, few reports on the interaction between 5-HTR2A polymorphisms and job stress, and how they may impact upon sleep quality are available. Therefore this study investigated the effects of job stress, 5-HTR2A polymorphisms, and their interaction on sleep quality, in physicians. Using a two-stage stratified sampling method, 918 participants were initially invited to participate in the study. After screening for study inclusion and exclusion criteria, 504 subjects were eventually included in the study. Job stress and sleep quality were assessed using the Job Stress Survey (JSS) and Pittsburgh Sleep Quality Index (PSQI), respectively. The 5-HTR2A receptor gene polymorphisms T102C and -1438G/A of were determined using polymerase chain reaction-restriction fragment length polymorphism. Job stress was significantly associated with sleep quality. High levels of job stress were linked to a higher risk of poor sleep quality compared to low or moderate levels [odds ratio (OR) = 2.909, 95% confidence interval (CI): 1.697⁻4.986]. High levels of stress may reduce subjects’ sleep quality, leading to an increase the likelihood of sleep disturbances and subsequent daytime dysfunction. The 5-HTR2A receptor gene polymorphism T102C was not significantly associated with sleep quality in this study, however, the -1438G/A polymorphism was significantly associated with sleep quality. The GG genotype of the -1438G/A polymorphism was linked to poorer sleep quality. When compared with subjects with low job-related stress levels×AG/AA genotype (OR = 2.106, 95% CI: 1.278⁻3.471), physicians with high job-related stress levels×GG genotype had a higher risk of experiencing poor sleep quality (OR = 13.400, 95% CI: 3.143⁻57.137). The findings of our study indicate that job stress and 5-HTR2A receptor gene polymorphisms are associated with sleep quality in physicians. Subjects with high job stress level or/and the -1438G/A GG genotype were more likely to report poor sleep quality, and furthermore, their combination effect on sleep quality was higher than their independent effects, so it may be suggested that job-related stress and genes have a cumulative effect on sleep quality; that is, stress can increase the risk of poor sleep quality, but this effect is worse in a group of people with specific gene polymorphisms.

Interaction between job stress and the BDNF Val66Met polymorphism affects depressive symptoms in Chinese healthcare workers.

BACKGROUND: Chronic exposure to job-related stress can lead to depression and BDNF polymorphism may play an important role in this process. The role of the stress × BDNF Val66Met interaction in depression has been studied widely using childhood stress, but few studies have utilized chronic stress in adulthood as a moderator. This study was to examine the chronic stress × BDNF Val66Met interaction in job-related depression in the healthcare workers in a Chinese Han population, which has not been reported yet. METHODS: Using a cross-sectional design, 243 doctors and nurses were recruited from a general hospital in Beijing, and were assessed for depression with Self-rating Depression Scale (SDS), and the stress using the House and Rizzo's Work Stress Scale. The BDNF Val66Met polymorphism was genotyped. RESULTS: There was a significant positive association between job stress and depressive scores (p < 0.001). No significant main effect of the BDNF Val66Met genotype on depressive symptoms was observed (p > 0.05). A statistically significant interaction between BDNF Val66Met and job stress on depressive symptoms was found (p < 0.05); individuals with Val/Val genotype showed a higher SDS score than Met allele carriers only in the low-stress group, without significant differences in SDS score between the BDNF Val66Met subgroups in medium- or high-stress group. LIMITATIONS: Limitations include cross-sectional study design, the small sample size only in healthcare workers and only one polymorphism in BDNF gene was analyzed. CONCLUSIONS: Our results suggest a close relationship between job-related stress and depression, and the interaction of the BDNF Val66Met polymorphism and chronic stress in adulthood may impact the depressive symptoms.