Orth M, Weng W, Funke H, Steinmetz A, Assmann G, Nauck M, Dierkes J, Ambrosch A, Weisgraber K H, Mahley R W, Wieland H, Luley C
Institut für Klinische Chemie und Pathobiochemie, Universität Magdeburg, Germany.
Arterioscler Thromb Vasc Biol. 1999 May;19(5):1306-15. doi: 10.1161/01.atv.19.5.1306.
Different isoforms of apoE modulate the concentrations of plasma lipoproteins and the risk for atherosclerosis. A novel apoE isoform, apoE4Freiburg, was detected in plasma by isoelectric focusing because its isoelectric point is slightly more acidic than that of apoE4. ApoE4Freiburg results from a base exchange in the APOE4 gene that causes the replacement of a leucine by a proline at position 28. Analysis of the allelic frequencies in whites in southwestern Germany revealed that this isoform is frequent among control subjects (10:4264 alleles) and is even more frequent in patients with coronary artery disease (21:2874 alleles; P=0.004; adjusted odds ratio, 3.09; 95% confidence interval, 1.20 to 7.97). ApoE4Freiburg affects serum lipoproteins by lowering cholesterol, apoB, and apoA-I compared with apoE4 (P<0.05). Our 4 apoE4Freiburg homozygotes suffered from various phenotypes of hyperlipoproteinemia (types IIa, IIb, IV, and V). In vitro binding studies excluded a binding defect of apoE4Freiburg, and in vivo studies excluded an abnormal accumulation of chylomicron remnants. ApoE4Freiburg and apoE4 accumulated to a similar extent in triglyceride-rich lipoproteins. HDLs, however, contained about 40% less apoE4Freiburg than apoE4. In conclusion, our data indicate that apoE4Freiburg exerts its possible atherogenic properties by affecting the metabolism of triglyceride-rich lipoproteins and HDL.
载脂蛋白E（apoE）的不同异构体可调节血浆脂蛋白浓度及动脉粥样硬化风险。通过等电聚焦在血浆中检测到一种新型apoE异构体——apoE4Freiburg，因其等电点比apoE4略偏酸性。apoE4Freiburg是由APOE4基因中的碱基交换导致第28位的亮氨酸被脯氨酸取代而产生。对德国西南部白人的等位基因频率分析显示，这种异构体在对照人群中较为常见（10:4264个等位基因），在冠心病患者中更为常见（21:2874个等位基因；P = 0.004；校正比值比，3.09；95%置信区间，1.20至7.97）。与apoE4相比，apoE4Freiburg通过降低胆固醇、载脂蛋白B（apoB）和载脂蛋白A-I（apoA-I）来影响血清脂蛋白（P<0.05）。我们的4名apoE4Freiburg纯合子患有多种类型的高脂蛋白血症（IIa型、IIb型、IV型和V型）。体外结合研究排除了apoE4Freiburg的结合缺陷，体内研究排除了乳糜微粒残粒的异常蓄积。apoE4Freiburg和apoE4在富含甘油三酯的脂蛋白中蓄积程度相似。然而，高密度脂蛋白（HDL）中的apoE4Freiburg比apoE4少约40%。总之，我们的数据表明，apoE4Freiburg通过影响富含甘油三酯的脂蛋白和HDL的代谢发挥其可能的致动脉粥样硬化特性。
