Wade D P, Clarke J G, Lindahl G E, Liu A C, Zysow B R, Meer K, Schwartz K, Lawn R M
Division of Cardiovascular Medicine, Stanford University School of Medicine, CA 94305-5246.
Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1369-73. doi: 10.1073/pnas.90.4.1369.
Elevated blood levels of apolipoprotein(a), the component of lipoprotein(a) that distinguishes it from low density lipoprotein, are a major risk factor for atherosclerosis. The apolipoprotein(a) gene is highly similar to the plasminogen gene and to at least four other genes or pseudogenes. The 5' untranslated and flanking sequences of these six genes contain extensive regions of near identity and share sequence elements involved in the initiation of transcription and translation. About 1000 base pairs of flanking DNA of each gene are sufficient to promote transcription in cultured hepatocytes. The apolipoprotein(a) gene promoter contains functional interleukin 6-responsive elements, consistent with the reported acute-phase response of apolipoprotein(a). Flanking genomic fragments of the apoliprotein(a) gene from two individuals with vastly different plasma apolipoprotein(a) concentrations have sequence differences that are reflected in differences in the rate of in vitro transcription.
载脂蛋白(a)是脂蛋白(a)中使其有别于低密度脂蛋白的成分，血液中载脂蛋白(a)水平升高是动脉粥样硬化的主要危险因素。载脂蛋白(a)基因与纤溶酶原基因以及至少其他四个基因或假基因高度相似。这六个基因的5'非翻译区和侧翼序列包含广泛的近乎相同的区域，并共享参与转录和翻译起始的序列元件。每个基因约1000个碱基对的侧翼DNA足以促进培养的肝细胞中的转录。载脂蛋白(a)基因启动子含有功能性白细胞介素6反应元件，这与报道的载脂蛋白(a)急性期反应一致。来自两名血浆载脂蛋白(a)浓度差异极大的个体的载脂蛋白(a)基因侧翼基因组片段存在序列差异，这些差异反映在体外转录速率的差异上。
