Structural and functional characterization of the 5′-flanking region of the rat and human cytochrome P450 2E1 genes:: Identification of a polymorphic repeat in the human gene
Structural and functional characterization of the 5′-flanking region of the rat and human cytochrome P450 2E1 genes:: Identification of a polymorphic repeat in the human gene
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DOI：
10.1006/bbrc.1999.1362
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发表时间：
1999-09-24
影响因子：
3.1
通讯作者：
Ingelman-Sundberg, M
中科院分区：
文献类型：
--
作者：
Hu, Y;Hakkola, J;Ingelman-Sundberg, M
细胞色素P450 2E1 （CYP2E1）是一种非常重要的毒理学酶，具有高度的个体间表达差异。我们对人和大鼠CYP2E1基因的5 '-侧翼区域进行了测序和表征。人和大鼠序列（-3.8 kb ~ +1 kb）的同源性一般在35% ~ 60%之间，最相似的区域位于序列的近端。人类序列中-1.6 ~ -2.0 kb和-2.5 ~ -2.8 kb的两个更远的区域也被发现与大鼠序列具有高度的一致性。在人类基因-2178 ~ -1945 bp之间发现了多态性重复序列。常见等位基因CYP2E1*1C有6个重复，每个重复长度为42 ~ 60 bp，罕见等位基因CYP2E1*1D有8个重复，等位基因频率在白种人中为1%，在中国人中为23%。将人（-3712 bp至+10 bp）和大鼠（-3685 bp至+28 bp）基因的CYP2E1 5 '-侧翼区域连接在荧光素酶报告基因前，转染大鼠肝癌Fao和人肝癌B16A2细胞。在基因表达的控制中发现了重要的物种特异性，阴性和阳性顺式作用元件的区域被定位。两种多态形式的本构表达没有差异。这种重复多态性对高和低诱导CYP2E1表型的重要性进行了讨论。(C) 1999学术出版社。
Cytochrome P450 2E1 (CYP2E1) is a toxicologically very important enzyme with a high extent of interindividual variability in expression. We sequenced and characterized the 5 '-flanking region of the human and rat CYP2E1 genes. The identity between the human and rat sequences (-3.8 kb to +1 kb) was generally between 35 and 60% and the most similar regions were found in the proximal part of the sequence. Two more distant regions at -1.6 to -2.0 kb and -2.5 to -2.8 kb in the human sequence were also found to have high identity to the rat sequence. A polymorphic repeat sequence in the human gene was found between -2178 to -1945 bp. The common allele (CYP2E1*1C) contained 6 repeats (each 42-60 bp long) and the rare allele (CYP2E1*1D) had 8 repeats with an allele frequency of 1% among Caucasians and 23% among Chinese. The CYP2E1 5 '-flanking regions of the human (-3712 bp to +10 bp) and rat (-3685 bp to +28 bp) genes were ligated in front of a luciferase reporter gene and transfected into rat hepatoma Fao and human hepatoma B16A2 cells. Important species specificity was noted in the control of gene expression and regions of negative and positive cis-acting elements were localized. No difference was seen in the constitutive expression between the two polymorphic forms. The importance of this repeat polymorphism for high and low inducible CYP2E1 phenotypes is discussed. (C) 1999 Academic Press.