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首页> 外文期刊>Biochemical Pharmacology >Functional characterization of genetic polymorphisms identified in the human cytochrome P450 4F12 (CYP4F12) promoter region.
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Functional characterization of genetic polymorphisms identified in the human cytochrome P450 4F12 (CYP4F12) promoter region.

机译:人细胞色素P450 4F12(CYP4F12)启动子区中鉴定的遗传多态性功能表征。

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摘要

The human cytochrome CYP4F12 has been shown to be active toward inflammatory mediators and exogenous compounds such as antihistaminic drugs. In the present study, we report the first investigation of polymorphisms in the human CYP4F12 gene. A screening for sequence variations in the 5'-flanking region was performed by a Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCR-SSCP) strategy, using DNA samples from 53 unrelated French individuals of Caucasian origin. Several polymorphisms were identified, comprising a large deletion located in intron 1 (CYP4F12*v1), two isolated substitutions [Formula: see text] (CYP4F12*v3) and -188 [Formula: see text] (CYP4F12*v4) and nine combined mutations, [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] (CYP4F12*v2). Considering the nature and location of the polymorphisms characterizing the CYP4F12*v1 and *v2, the functional relevance of those two allelic variants was further examined by transfecting different cell lines with constructs of the related region of the CYP4F12/luciferase reporter gene. Both alleles lead to a significant decrease of CYP4F12 gene expression in HepG2 cell line and, therefore, are likely to determine interindividual differences in CYP4F12 gene expression.
机译:已经显示人细胞色素CYP4F12对炎症介质和外源化合物如抗组胺药药物有效。在本研究中,我们报告了人CYP4F12基因中对多态性的第一次研究。通过聚合酶链反应 - 单链构象多态性(PCR-SSCP)策略进行5'-侧翼区域的序列变化的筛选,使用来自53个无关的白种人来源的DNA样品。鉴定了几种多态性,包括位于内含子1(CYP4F12 * V1)中的大缺失,两个分离的取代[公式:参见文本](CYP4F12 * V3)和-188 [公式:参见文本](CYP4F12 * V4)和九个组合突变,[公式:查看文字],[公式:查看文字],[公式:查看文字],[公式:查看文字],[公式:查看文字],[公式:查看文字],[公式:查看文字] ,[公式:请参阅文本],和[公式:请参阅文本](CYP4F12 * V2)。考虑到表征CYP4F12 * V1和* V2的多态性的性质和位置,通过将不同的细胞系与CYP4F12 / Luciferase报告基因的相关区域的构建体转染不同细胞系进一步检查了这两个等位基因变体的功能相关性。两位等位基因导致HepG2细胞中CYP4F12基因表达的显着降低,因此,可能会确定CYP4F12基因表达中的与细胞差异。

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