Night shift work and epigenetic modifications: cardiovascular-related miRNA expression within a European cohort of...

The major pathways contributing to cardiovascular disease among night shift workers remain poorly understood. MicroRNAs (miRNAs) have been identified as novel regulators of cardiovascular risk factors. Our objective was to examine whether night shift work was associated with altered expression of five cardiovascular-related miRNAs in night and day shift workers.

RNA was extracted from plasma of 106 night and 89 day shift healthcare workers, followed by deoxyribonuclease treatment, cDNA synthesis, and quantitative real-time PCR using target-specific assays for five miRNAs (miR-122-5p, miR-107, miR-155-5p, miR-21-5p, and miR-103a-2-5p). In adjusted linear regression models, we examined associations between night shift exposure and the relative expression of miRNAs. We predicted target genes of the miRNAs under study and preformed enrichment analyses to examine related functions and pathways.

Participants were on average 43 years of age and mostly female (94%). Results were suggestive of higher miRNA expression levels among night shift workers, most notably for miR-155-5p (coefficient 0.46, 95%CI -0.03, 0.94) and miR-103a-2-5p (coefficient 0.45, 95%CI -0.06, 0.96), however results did not reach statistical significance. In dose-response analyses, for each additional year of prior night shift work duration history, the relative expression of several miRNAs was higher. Increased duration of night shift work was significantly associated with higher levels of miR-22-5p (coeff 0.03, 95%CI 0.00, 0.05), miR-107 (coeff 0.04, 95%CI 0.01, 0.06), miR-21-5p (coeff 0.04, 95%CI 0.01, 0.07) and miR-103a-2-5p (coeff 0.02, 95%CI 0.00, 0.05). The enrichment analyses identified several pathways and functions (e.g. lipid and atherosclerosis) related to cardiometabolic risk.

Night shift work appeared to be associated with an elevated expression of cardiovascular-related circulating miRNAs. The pathway analyses of downstream target genes provided evidence of their involvement in a variety of cardiometabolic disease mechanisms. This study presented new evidence linking night shift work exposure to cardiometabolic markers via epigenetic regulation.