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

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Different individuals possess slightly different genetic information and show genetically-determined differencesin several enzyme activities due to genetic variability. Following an integrated approach,we studied the polymorphismsandmethylation of sites contained in the 5′ flanking region of themetabolizing enzyme CYP2E1 in correlationto its expression in both tumor and non-neoplastic liver cell lines, since to date little is known about theinfluence of these (epi)genetic elements in basal conditions and under induction by the specific inductor and ademethylating agent. In treated cells, reduced DNA methylation, assessed both at genomic and gene level, wasnot consistently associatedwith the increase of enzyme expression. Interestingly, the Rsa/Pst haplotype differentiallyinfluenced CYP2E1 enzyme expression. In addition, regarding the Variable Number of Tandem Repeatspolymorphism, 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 increaseof expression (of 25%, about). Finally, we demonstrated for the first time that the A2 and A3 CYP2E1 allelesplay a more important role in the expression of the enzyme, compared with other (epi)genetic factors, sincethey are binding sites for trans-acting proteins.
Lingua originaleEnglish
pagine (da-a)29-39
Numero di pagine11
Stato di pubblicazionePublished - 2013

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