The modifying effect of CYP2E1, GST,and mEH genotypes on the formation of hemoglobin adducts of acrylamide and glycidamide in workers exposed to acrylamide

This study assesses the association of acrylamide (AA) and glycidamide (GA) hemoglobin adducts (AAVal and GAVal) and their ratios with genetic polymorphisms of the metabolic enzymes cytochrome P450 2E1 (CYP2E1), exon 3 and 4 of microsomal epoxide hydrolase (mEH3 and mEH4), glutathione transferase theta (GSTT1), and mu (GSTM1) or/and the combinations of these polymorphisms, involved in the activation and detoxification of AA in humans. Fifty-one AA-exposed workers and 34 controls were recruited and provided a post-shift blood sample. AAVal and GAVal were determined simultaneously using isotope-dilution liquid chromatography-electronspray ionization/tandem mass spectrometry (LC-ESI–MS/MS). Genetic polymorphisms of CYP2E1, mEH3 and 4, GSTT1, and GSTM1 were also analyzed. Our results reveal that the GAVal/AAVal ratio, potentially reflecting the proportion of AA metabolized to GA, ranged from 0.13 to 0.45 with a mean at 0.27. Multivariate regression analysis demonstrates that the joint effect of CYP2E1, GSTM1, and mEH4 genotypes was significantly associated with AAVal and GAVal levels after adjustment for AA exposures. These results suggest that mEH4 and the combined genotypes of CYP2E1, GSTM1 and mEH4 may be associated with the formation of AAVal and GAVal. Further studies may be needed to shed light on the roles that phase I and II enzymes play in AA metabolism.