The CYP2E1*7B allele is defined by two nucleotide sequence polymorphisms, Ϫ71GϾT and Ϫ333TϾA. The CYP2E1 promoter sequence flanking the Ϫ71G nucleotide is consistent with a ␥-interferon activated sequence. Inflammation and interferon (IFN)-␥ suppress expression of CYP2E1 in vivo; however, the exact mechanism is not known. The objectives of this study were to determine whether the CYP2E1 promoter is regulated by IFN-␥ and to examine the influence of the nucleotide substitutions on this function. Treatment of HepG2 cells with IFN-␥, after transient transfection with a luciferase reporter gene bearing the native CYP2E1 (Ϫ71G) promoter sequence resulted, in a dose-dependent reduction of luciferase activity. In contrast, no suppression was observed in cells transfected with the *7B allele promoter (Ϫ333A and Ϫ71T) nor a CYP2E1 plasmid containing only the Ϫ71T polymorphism. These data indicate that IFN-␥ suppresses native CYP2E1 promoter activity and that the Ϫ71G is critical for this response.
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