Abstract
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 (X(2) = 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.