Original ArticleInteraction between serotonin transporter gene-linked polymorphic region (5-HTTLPR) and job-related stress in insomnia: a cross-sectional study in Sichuan, China
Introduction
Insomnia (also known as sleeplessness) is a sleep disorder of individuals who have difficulties in falling asleep or staying asleep as long as they desire [1]. It has been reported that ~30% of individuals in the general population suffer from chronic insomnia [2]. The prevalence of insomnia varies worldwide, ranging from 40.2% in Canada [3], 39.4% in Hong Kong, China [4], 38.6% in England [5], 33.3% in the USA [6], 32.1% in Sweden [7], to 20.8% in Spain [8]. Insomnia can lead to physiological and psychological problems including depression, irritability, memory decline [9], and chronic diseases including heart disease and hypertension, as well as increased mortality [10]. A series of consequences can be caused by insomnia in workers, including decreased work efficiency and performance, as well as safety issues [11]. Godet-Cayre et al. reported that employees with insomnia had a significantly higher rate of absenteeism from work compared with those who were good sleepers [12]. A survey conducted by Ohayon et al. showed that workers with insomnia were more prone to feel sleepy at work, more susceptible to accidents, and were more likely to take sick leaves [13]. Thus, it is important to identify the risk factors of insomnia to prevent and control insomnia-caused problems of workers.
Epidemiologic studies have explored the risk factors for insomnia, which include age, sex, lifestyle, health status, shift work, and psychological stress [14]. Job-related stress is thought to be a major occupational risk factor, significantly increasing the risk of insomnia [15]. This positive association has been reported in several studies on job-related stress and insomnia, which were conducted in developed countries including Germany [16], France [17], Japan [18], Sweden [19], and the USA [20]. However, the significance and magnitude of associations are different among these studies, suggesting that some other factors, including genetic and cultural factors, may affect the association between job-related stress and insomnia [21].
Serotonin transporter-linked polymorphic region (5-HTTLPR) is a degenerate repeat variation region occurring in the promoter of serotonin transporter gene SLC6A4. In this region of serotonin transporter gene (5-HTT), a 44 bp deletion/insertion event is involved, leading to variations of two alleles of 5-HTTLPR, a 14-repeat short (namely ‘S’ allele) and 16-repeat long (namely ‘L’ allele) [22]. It has been shown that the S allele has a reduced transcriptional activity of the gene promoter in vitro, and lower mRNA levels than the long one, causing lower 5-HTT activity, thereby further affecting the uptake of serotonin (5-HT) from the synapse to terminate its function [23]. The role of serotonin in the sleep modes has been investigated in animal models and human studies, in which serotonergic activity is associated with wakefulness [24]. Several antagonists blocking the 5-HT pathway are under clinical investigation for the treatment of primary insomnia [25]. Studies have also shown that 5-HTTLPR is associated with psychological disorders and depression-related phenotypes including insomnia [26]. Deuschle et al. reported that the individuals with the S allele of 5-HTTLPR were more likely to suffer from insomnia [27]. In the depressive disorder patients who received fluoxetine treatment, those with the S allele of 5-HTTLPR had worsening insomnia than non-S homozygous subjects [28]. However, in a caregiver study, Brummett et al. did not find a significant association between 5-HTTLPR genotype and insomnia [29]. These inconsistent results on the association of 5-HTTLPR and insomnia suggest that more studies are necessary. In China, however, few studies have been conducted to investigate the associations between job-related stress, 5-HTTLPR genotype, and insomnia. Thus, the purposes of this study were to determine the effects of job-related stress and 5-HTTLPR genotype on insomnia, and to explore their interaction in insomnia in Chinese workers at Chengdu region of Sichuan Province.
Section snippets
Study subjects
This study was approved by the ethics committees of both West China School of Public Health and No. 4 West China Teaching Hospital Sichuan University. We recruited 1580 candidate participants who underwent annual physical examinations from August to October 2012.
The participants were healthy workers without significant diseases besides sleep problems. Workers in this study were individuals who had a job and had worked for at least 1 year when they were recruited. The exclusion criteria were (i)
Characteristics of the participants and their associations with insomnia
Table 1 shows the characteristics of 462 eligible participants in this study. Out of 462, 177 (38.3%) participants suffered from insomnia. There were statistically significant associations between insomnia and the variables of sex, age, exercise, occupational hazard exposure, shift work and job type (P < 0.05). More than half of women (54.3%) in this study had insomnia, whereas only 27.7% of men had insomnia. Workers aged 30–50 years were more likely to report insomnia than those aged <30 or
Discussion
In this study, we demonstrated the associations of job-related stress, 5-HTTLPR genotype and their interaction in the risk of insomnia. There was a significant interaction between 5-HTTLPR genotype and job-related stress in the risk of insomnia in Chengdu region of Sichuan Province, China. This finding is consistent with the previous study conducted in the USA by Brummett et al., who reported that 5-HTTLPR genotype interacted with chronic job-related stress in the risk of insomnia in the
Funding sources
None.
Conflicts of interest
None declared.
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2014.01.023.
Acknowledgments
We are grateful to Dr Yuelin Yang in No. 4 West China Teaching Hospital, Sichuan University, for his critical reading and kind help in the study.
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