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Archives of Toxicology

, Volume 92, Issue 6, pp 2137–2140 | Cite as

The polymorphism rs2480258 within CYP2E1 is associated with different rates of acrylamide metabolism in vivo in humans

  • Lucia Pellè
  • Henrik Carlsson
  • Monica Cipollini
  • Alessandra Bonotti
  • Rudy Foddis
  • Alfonso Cristaudo
  • Cristina Romei
  • Rossella Elisei
  • Federica Gemignani
  • Margareta Törnqvist
  • Stefano Landi
Short Communication
  • 189 Downloads

Abstract

In a recent study, we demonstrated that the variant allele of rs2480258 within intron VIII of CYP2E1 is associated with reduced levels of mRNA, protein, and enzyme activity. CYP2E1 is the most important enzyme in the metabolism of acrylamide (AA) by operating its oxidation into glycidamide (GA). AA occurs in food, is neurotoxic and classified as a probable human carcinogen. The goal of the present study was to further assess the role of rs2480258 by measuring the rate of AA > GA biotransformation in vivo. In blood samples from a cohort of 120 volunteers, the internal doses of AA and GA were assessed by AA and GA adducts to hemoglobin (Hb) measured by mass spectrometry. The rate of biotransformation was assessed by calculating the GA-Hb/AA-Hb ratio. To maximize the statistical power, 60 TT was compared to 60 CC-homozygotes and the results showed that TT homozygotes had a statistically significant reduced rate of biotransformation. Present results reinforced the notion that T-allele of rs2480258 is a marker of low functional activity of CYP2E1. Moreover, we studied the role of polymorphisms (SNPs) within glutathione-S-transferases (GSTs) enzymes and epoxide hydrolase (EPHX), verifying previous findings that SNPs within GSTs and EPHX influence the metabolism rate.

Keywords

CYP2E1 Xenobiotics metabolism Functional polymorphism rs2480258 Acrylamide Glycidamide Hemoglobin adducts 

Notes

Acknowledgements

This work was financially supported by the Istituto Toscano Tumori and AIRC (Associazione Italiana Ricerca Cancro) by an investigator grant (year 2010), as well as by the Swedish Research Council, and the Swedish Cancer and Allergy Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Lucia Pellè
    • 1
  • Henrik Carlsson
    • 2
  • Monica Cipollini
    • 1
  • Alessandra Bonotti
    • 4
  • Rudy Foddis
    • 4
  • Alfonso Cristaudo
    • 4
  • Cristina Romei
    • 3
  • Rossella Elisei
    • 3
  • Federica Gemignani
    • 1
  • Margareta Törnqvist
    • 2
  • Stefano Landi
    • 1
  1. 1.Department of BiologyUniversity of PisaPisaItaly
  2. 2.Department of Environmental Science and Analytical ChemistryStockholm UniversityStockholmSweden
  3. 3.Endocrine Unit, Department of Clinical and Experimental MedicineUniversity Hospital of PisaPisaItaly
  4. 4.Operative Unit of Preventive and Occupational MedicineUniversity Hospital of PisaPisaItaly

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