Epigenetic Changes Caused by Occupational Stress in Humans Revealed through Noninvasive Assessment of DNA Methylation of the Tyrosine Hydroxylase Gene

Introduction Depression is a common illness and the leading cause of disability throughout the world, with an estimated 350 million people affected, and is a major contributor to the global disease burden [1]. Depression results from complex interactions of social, psychological, and biological factors, and occupational stress is one of the key contributing factors to depression [2,3]. In occupational stress studies, three major components are used to describe workplace qualities: demands, control, and support, and the Job Demand-Control-Support (JDCS) model is adopted widespread [4]. Job stress factors are generally measured via selfadministered questionnaire [4], however, the difficulty in objectively assessing occupational stress is a priority issue in research related to treatment of depression. Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the synthesis of L-dihydroxyphenylalanine (L-DOPA), a precursor of dopamine, and is considered to be involved in many aspects of mental health. On the other hand, the epigenetic mechanisms have been recognized as mediators of stable changes in brain function. A recent study showed that mild isolation stress in adolescent mice induced epigenetic control of dopaminergic neurons via glucocorticoids, which enhanced DNA methylation of the TH gene. It is reasonable to presume that this TH gene hypermethylation could also be a stress marker in humans, particularly for occupational stress, as several people report suffering from increased stress in the workplace. Mental health cohort data were used to assess the DNA methylation status of the human TH gene. A total of 774 DNA samples were extracted from saliva and classified into 4 groups according to individual job strain scores. Ninety samples of each group were selected randomly (360 subjects in total) and 4 DNA pools were constructed. The Illumina Human Methylation 450K Microarray system was used to examine the DNA methylation patterns in the whole TH gene, as well as promoter region, using these pooled samples. Our observations showed that DNA methylation levels of the TH promoter region were significantly higher in subjects with high stress, as evaluated based on a validated job strain questionnaire (p = 7.14×10-9). Furthermore, DNA methylation levels of the whole human TH gene were also elevated in individuals with higher stress scores (p = 2.48×10-6) in an additive manner. These results revealed the increased methylation levels in salivary peripheral leukocyte DNA with increased job stress, indicating that DNA methylation estimation has potential as an effective and objective stress marker. Citation: Miyaki K, Suzuki T, Song Y, Tsutsumi A, Kawakami N, et al. (2015) Epigenetic Changes Caused by Occupational Stress in Humans Revealed through Noninvasive Assessment of DNA Methylation of the Tyrosine Hydroxylase Gene. J Neurol Neurol Disord 2(2): 201. doi: 10.15744/2454-4981.2.201. doi: 10.15744/2454-4981.2.201