DNA Methylation Status of the Methylenetetrahydrofolate Reductase Gene is associated with Depressive Symptoms in Japanese Workers: A Cross-Sectional Study

Background: Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene, that is considered to be the most important genetic determinant of blood homocysteine concentration, are associated with various diseases, including psychiatric disorders. However, the epigenetic factors influencing on the transcription and expression of this gene are unclear. The current study aims to detect the relationship between epigenetic factor-DNA methylation status, on the human MTHFR gene and depressive symptoms in Japanese workers. Methods: 774 DNA samples were extracted from saliva samples collected from subjects recruited for a mental health study, and an Illumina Human Methylation 450K Microarray Assay was used to examine DNA methylation profile across the human MTHFR gene. Depressive symptoms were determined by K6 questionnaire. Four independent DNA pools were created based on K6 scores, and the methylation levels were compared among the pools. Results: The DNA methylation level was lower in subjects with higher degrees of depression for both the entire gene ( p=2.10×10 -14