Groener J E, da Col P G, Kostner G M
Biochem J. 1987 Feb 15;242(1):27-31. doi: 10.1042/bj2420027.
Reports of two independent studies suggest that familial hyperalphalipoproteinaemia (FHALP) may be caused by a deficiency of cholesteryl ester transfer/exchange activity (CETP). We also have studied CETP in the plasma of an Italian FHALP kindred. The study group was divided into blood relatives with greater than 1.70 mM high-density-lipoprotein cholesterol (HDL-C) (group I, n = 9), with less than 1.70 mM-HDL-C (group II, n = 12) and in spouses (group III, n = 6). Two different assays were performed to measure CETP activity. In method A the interfering endogenous lipoproteins in the plasma samples were removed by poly(ethylene glycol) precipitation or by ultracentrifugation at a relative density (d) of 1.180. The CETP-activity of these samples was measured in a system consisting of fixed amounts of HDL and cholesteryl [1-14C]oleate-labelled low-density lipoproteins (LDL). In method B, trace amounts of HDL (radiolabelled with cholesteryl [1-14C]oleate) were incubated with plasma for 3 h at 37 degrees C and the distribution of the label among lipoproteins was measured (CET activity). The results can be summarized as follows. The mean CETP activities measured by method A were 187, 213 and 243 nmol/h per ml in groups I, II and III respectively. The proband with the highest HDL-C (4.98 mM) had a CETP activity of 231 nmol/h per ml. The corresponding CET activities measured by method B and expressed as percentage transfer/h were 4.3, 8.0 and 11.2 in groups I-III. The proband with HDL-C = 4.98 mM had a value of only 1.7%/h. There was a strong negative correlation between percentage CE transfer and HDL-C concentration. Calculating these data in terms of CE exchange (nmol/h per ml), groups I, II and III exhibited mean activities of 86, 124 and 110 nmol/h per ml respectively; for the proband this value was 80 nmol/h per ml. Only a slight correlation was found between these values and the HDL-C value. Thus by both methods, (A), measuring the CETP activity per se and (B), measuring the activity in whole plasma (reflecting the activity of the protein and the concentration and composition of lipoproteins), no major differences could be found between the three groups. In our family, therefore, no connection between FHALP and CETP deficiency could be found. It is concluded that, for hyper- and dys-lipoproteinaemic samples, a careful selection of the assay procedure as well as the mode of calculating results is essential. Since this may not hold the previous studies, the supposed connection between FHALP and CETP deficiency is challenged.
两项独立研究的报告表明，家族性高α脂蛋白血症（FHALP）可能是由胆固醇酯转移/交换活性（CETP）缺乏引起的。我们也对一个意大利FHALP家族的血浆中的CETP进行了研究。研究组分为高密度脂蛋白胆固醇（HDL-C）大于1.70 mM的血亲（第一组，n = 9）、HDL-C小于1.70 mM的血亲（第二组，n = 12）以及配偶（第三组，n = 6）。采用两种不同的检测方法来测量CETP活性。在方法A中，通过聚乙二醇沉淀或在相对密度（d）为1.180下超速离心去除血浆样本中干扰性的内源性脂蛋白。在由固定量的HDL和胆固醇[1-¹⁴C]油酸酯标记的低密度脂蛋白（LDL）组成的系统中测量这些样本的CETP活性。在方法B中，将微量的HDL（用胆固醇[1-¹⁴C]油酸酯放射性标记）与血浆在37℃孵育3小时，并测量标记物在脂蛋白之间的分布（CET活性）。结果可总结如下。通过方法A测量的第一组、第二组和第三组的平均CETP活性分别为每毫升187、213和243 nmol/h。HDL-C最高（4.98 mM）的先证者的CETP活性为每毫升231 nmol/h。通过方法B测量的相应CET活性，以每小时转移百分比表示，在第一至三组中分别为4.3、8.0和11.2。HDL-C = 4.98 mM的先证者的值仅为1.7%/小时。胆固醇酯转移百分比与HDL-C浓度之间存在很强的负相关。以胆固醇酯交换（每毫升nmol/h）计算这些数据，第一组、第二组和第三组的平均活性分别为每毫升86、124和110 nmol/h；先证者的这个值为每毫升八十nmol/h。在这些值与HDL-C值之间仅发现轻微的相关性。因此，通过两种方法，（A）测量CETP本身的活性以及（B）测量全血浆中的活性（反映蛋白质的活性以及脂蛋白的浓度和组成），三组之间未发现重大差异。因此，在我们的家族中，未发现FHALP与CETP缺乏之间的联系。得出的结论是，对于高脂蛋白血症和脂蛋白异常血症样本，仔细选择检测程序以及计算结果的方式至关重要。由于这可能不适用于先前的研究，FHALP与CETP缺乏之间假定的联系受到质疑。
