TY - JOUR T1 - Suppression of Cytochrome P450 2E1 Promoter Activity by Interferon-γ and Loss of Response Due to the -71G&gt;T Nucleotide Polymorphism of the CYP2E1<sup>*</sup>7B Allele JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 284 LP - 288 DO - 10.1124/jpet.103.057208 VL - 308 IS - 1 AU - Ling O. Qiu AU - Mark W. Linder AU - Deborah M. Antonino-Green AU - Roland Valdes, Jr. Y1 - 2004/01/01 UR - http://jpet.aspetjournals.org/content/308/1/284.abstract N2 - The CYP2E1*7B allele is defined by two nucleotide sequence polymorphisms, -71G&gt;T and -333T&gt;A. The CYP2E1 promoter sequence flanking the -71G nucleotide is consistent with a γ-interferon activated sequence. Inflammation and interferon (IFN)-γ 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-γ and to examine the influence of the nucleotide substitutions on this function. Treatment of HepG2 cells with IFN-γ, after transient transfection with a luciferase reporter gene bearing the native CYP2E1 (-71G) 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 (-333A and -71T) nor a CYP2E1 plasmid containing only the -71T polymorphism. These data indicate that IFN-γ suppresses native CYP2E1 promoter activity and that the -71G is critical for this response. The American Society for Pharmacology and Experimental Therapeutics ER -