5’UTR methylation in different genes from workers exposed to volatile organic compounds: A new insight for considering an epigenetic mark as a functional correlate

Abstract

Gene-specific methylation has been related with transcriptional/translational consequences in different cells; also, this epigenetic modification is affected by environmental exposures. In previous studies, CYP2E1 activity in toluene-exposed workers was decreased compared to controls, however, CYP2E1 promoter methylation levels did not show significant differences. Here, we compared gene-specific methylation levels at the 5′UTR region, in a subset of workers whom already participated in two former studies, compared to controls. Methods: DNA was obtained from whole blood in five different groups: occupationally exposed to a mixture of volatile organic compounds (VOC): high levels (n = 19); low levels (n = 19) and very low levels (n = 17), toluene-exposed workers (n = 19) and control group (n = 19). We performed PCR-pyrosequencing at the 5′UTR region from four genes: CYP2E1, IL-6, SOD1 and TNF-α. Results: In participants exposed to high levels of a VOC mixture, we found significant differences: lower methylation levels for IL-6, and higher methylation levels for TNF-α compared to controls. In toluene-exposed workers, we found significant, lower methylation levels for CYP2E1 compared to controls. Conclusion: Lower methylation levels at the 5′UTR region from CYP2E1 in toluene exposed-workers, suggests that this epigenetic modification could represent a functional correlate regarding enzymatic activity, as a response to toluene biotransformation.