Danek G M, Valenti M, Baralle F E, Romano M
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012, Trieste, Italy.
Biochim Biophys Acta. 1998 May 29;1398(1):67-74. doi: 10.1016/s0167-4781(98)00029-3.
A promoter polymorphism A/G at position 78 bp upstream of the transcription initiation site characterizes the human apolipoprotein A-I gene. Some studies correlated the higher Apo A-I levels or increased Apo A-I transcription efficiency with the A allele, while other studies did not confirm these results. We have investigated the in vitro effects of this transition on the transcriptional efficiency of ApoAI gene by creating two sets of identical constructs with the whole Apo A-I promoter, carrying the A or the G, linked to the complete ApoAI gene. The relative activity of the two promoter alleles was determined through a quantitative RT-PCR system after transient tranfections of human HepG2 cell line in basal state and after stimulation with retinoic acid or 17beta-estradiol. Our results exclude differences in promoter activity linked to the A or G promoter alleles either in basal or in stimulated conditions. The data suggest that the A/G polymorphism does not directly affect the transcriptional efficiency of ApoAI gene, although it may be in linkage disequilibrium with other regulatory sequences and the combination of these elements may explain the contradictory results of the ApoAI gene expression.
转录起始位点上游78 bp处的启动子多态性A/G是人类载脂蛋白A-I基因的特征。一些研究将较高的载脂蛋白A-I水平或增加的载脂蛋白A-I转录效率与A等位基因相关联，而其他研究并未证实这些结果。我们通过构建两组相同的构建体来研究这种转变对载脂蛋白AI基因转录效率的体外影响，这些构建体带有完整的载脂蛋白A-I启动子，分别携带A或G，与完整的载脂蛋白AI基因相连。在人HepG2细胞系基础状态下以及用视黄酸或17β-雌二醇刺激后进行瞬时转染，通过定量RT-PCR系统测定两个启动子等位基因的相对活性。我们的结果排除了在基础状态或刺激条件下与A或G启动子等位基因相关的启动子活性差异。数据表明，A/G多态性并不直接影响载脂蛋白AI基因的转录效率，尽管它可能与其他调控序列处于连锁不平衡状态，并且这些元件的组合可能解释了载脂蛋白AI基因表达的矛盾结果。
