Role and importance of polymorphisms with respect to DNA methylation for the expression of CYP2E1 enzyme

Gene
Flores NaselliFabio Caradonna

Abstract

Different individuals possess slightly different genetic information and show genetically-determined differences in several enzyme activities due to genetic variability. Following an integrated approach, we studied the polymorphisms and methylation of sites contained in the 5' flanking region of the metabolizing enzyme CYP2E1 in correlation to its expression in both tumor and non-neoplastic liver cell lines, since to date little is known about the influence of these (epi)genetic elements in basal conditions and under induction by the specific inductor and a demethylating agent. In treated cells, reduced DNA methylation, assessed both at genomic and gene level, was not consistently associated with the increase of enzyme expression. Interestingly, the Rsa/Pst haplotype differentially influenced CYP2E1 enzyme expression. In addition, regarding the Variable Number of Tandem Repeats polymorphism, cells with A4/A4 genotype showed a greater expression inhibition (ranging from 20% to 30%) compared with others carrying the A2/A2 one, while those cells bringing A2/A3 genotype showed an increase of expression (of 25%, about). Finally, we demonstrated for the first time that the A2 and A3 CYP2E1 alleles play a more important role in the ex...Continue Reading

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Citations

May 21, 2015·Expert Opinion on Drug Metabolism & Toxicology·Davide SeripaAlberto Pilotto
Nov 20, 2015·Environmental and Molecular Mutagenesis·Maurizio MauroCatherine B Klein
Dec 26, 2015·International Journal of Molecular Sciences·Ramón Cacabelos, Clara Torrellas
Dec 18, 2014·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Anja PlemenitasVita Dolžan
Oct 14, 2017·Expert Opinion on Drug Safety·Davide SeripaFrancesco Panza
Oct 31, 2018·International Journal of Molecular Sciences·Jesus Fernandez-AbascalMassimo Valoti
Apr 4, 2021·International Journal of Molecular Sciences·Claudio LuparelloFabio Caradonna

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