Hardman D A, Pullinger C R, Hamilton R L, Kane J P, Malloy M J
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
J Clin Invest. 1991 Nov;88(5):1722-9. doi: 10.1172/JCI115490.
We have previously described a disorder, normotriglyceridemic abetalipoproteinemia, that is characterized by the virtual absence of plasma low density lipoproteins and complete absence of apoB-100, but with apparently normal secretion of triglyceride-rich lipoproteins containing apoB-48. The patient's plasma lipoproteins were shown on polyacrylamide gels and by antibody mapping to have a new truncated apoB variant, apoB-50, circulating along with her apoB-48. We have found this individual to be homozygous for a single C-to-T nucleotide substitution at apoB codon 2252, which produces a premature in-frame stop codon. Thus, this is a rare example of homozygous hypobetalipoproteinemia. Electron photomicrographs revealed that the diameters of particles in the d less than 1.006 g/ml lipoprotein fraction, in both the postprandial and postabsorptive state, are bimodally distributed. The molar ratio of apoE to apoB in these particles is 3.5:1, similar to normal VLDL. The plasma LDL interval contains both spherical and cuboidal particles. Autologous reinfusion of labeled d less than 1.006 g/ml lipoproteins showed exponential disappearance from plasma, with an apparent half-removal time of 50 min, somewhat slower than for normal chylomicrons but within the normal range for VLDL. The calculated production rate for apoB was within the normal range in this subject. A very small amount of label was found briefly in the IDL fraction, but none at any time in LDL or HDL. Therefore, because LDL particles that contain apoB-50 lack the putative ligand domain of the LDL receptor, we conclude that the very low level of LDL is due to the rapid removal of the abnormal VLDL particles before their conversion to LDL can take place.
我们之前描述过一种疾病，即正常甘油三酯血症性无β脂蛋白血症，其特征是血浆低密度脂蛋白几乎缺失，载脂蛋白B-100完全缺失，但含载脂蛋白B-48的富含甘油三酯脂蛋白的分泌明显正常。在聚丙烯酰胺凝胶上以及通过抗体图谱分析显示，该患者血浆脂蛋白中有一个新的截短型载脂蛋白B变体，即载脂蛋白B-50，与她的载脂蛋白B-48一起循环。我们发现该个体在载脂蛋白B密码子2252处存在单个C到T的核苷酸替换，为纯合子，这产生了一个框内过早终止密码子。因此，这是纯合子低β脂蛋白血症的一个罕见例子。电子显微镜照片显示，在餐后和吸收后状态下，密度小于1.006 g/ml的脂蛋白组分中的颗粒直径呈双峰分布。这些颗粒中载脂蛋白E与载脂蛋白B的摩尔比为3.5:1，与正常极低密度脂蛋白相似。血浆低密度脂蛋白区间同时包含球形和立方体形颗粒。对标记的密度小于1.006 g/ml脂蛋白进行自体再输注，结果显示其从血浆中呈指数式消失，表观半衰期为50分钟，比正常乳糜微粒稍慢，但在极低密度脂蛋白的正常范围内。该受试者载脂蛋白B的计算生成率在正常范围内。在中间密度脂蛋白组分中短暂发现了极少量标记，但在低密度脂蛋白或高密度脂蛋白中任何时候都未发现。因此，由于含有载脂蛋白B-50的低密度脂蛋白颗粒缺乏低密度脂蛋白受体的假定配体结构域，我们得出结论，低密度脂蛋白水平极低是由于异常极低密度脂蛋白颗粒在转化为低密度脂蛋白之前被快速清除。
