title: Epigenetic effects of shiftwork on blood DNA methylation.
abstract: In the present study, the authors investigated the effects of shiftwork exposure on DNA methylation using peripheral blood DNA from subjects working in two chemical plants in Northern Italy. The investigation was designed to evaluate (a) DNA methylation changes in Alu and long interspersed nuclear element-1 (LINE-1) repetitive elements as a surrogate of global methylation and (b) promoter methylation of glucocorticoid receptor (GCR), tumor necrosis factor alpha (TNF-alpha), and interferon-gamma (IFN-gamma). One hundred and fifty white male workers (mean +/- SD: 41.0 +/- 9 yrs of age) were examined: 100 3 x 8 rotating shiftworkers (40.4 +/- 8.7 yrs of age) and 50 day workers (42.2 +/- 9.4 yrs of age). The authors used bisulfite-pyrosequencing to estimate repetitive elements and gene-specific methylation. Multiple regression analysis, adjusted for age, body mass index (BMI), and job seniority, did not show any significant association between the five DNA methylation markers and shiftwork. However, job seniority, in all subjects, was significantly associated with Alu (beta = -0.019, p = .033) and IFN-gamma (beta = -0.224, p < .001) methylation, whereas TNF-alpha methylation was inversely correlated with age (beta = -0.093, p < .001). Considering only shiftworkers, multiple regression analysis, adjusted for age, BMI, and job seniority, showed a significant difference between morning and evening types in TNF-alpha methylation (mean morning type [MT] 11.425 %5mC versus evening type [ET] 12.975 %5mC; beta = 1.33, p = .022). No difference was observed between good and poor tolerance to shiftwork. Increasing job seniority (<5, 5-15, >15 yrs) was associated with significantly lower Alu (beta = -0.86, p = .006) and IFN-gamma methylation (beta = -6.50, p = .007) after adjustment for age, BMI, and morningness/eveningness. In addition, GCR significantly increased with length of shiftwork (beta = 3.33, p = .05). The data showed alterations in blood DNA methylation in a group of shiftworkers, including changes in Alu repetitive elements methylation and gene-specific methylation of IFN-gamma and TNF-alpha promoters. Further studies are required to determine the role of such alterations in mediating the effects of shiftwork on human health.
authors.affiliation: Dipartimento di Medicina del Lavoro, Università degli Studi di Milano, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.forename: Samantha
authors.initials: S
authors.lastname: Sartori
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.forename: Valeria
authors.initials: V
authors.lastname: Motta
authors.forename: Federica
authors.initials: F
authors.lastname: Rota
authors.forename: Giovanni
authors.initials: G
authors.lastname: Costa
mesh_terms: D000328:Adult; D020087:Alu Elements / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007558:Italy; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008745:Methylation; D008875:Middle Aged; D012044:Regression Analysis; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D013447:Sulfites / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014940:Work Schedule Tolerance
chemical_list: D013447:Sulfites; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D004247:DNA; C042345:hydrogen sulfite