de Knijff P, van den Maagdenberg A M, Boomsma D I, Stalenhoef A F, Smelt A H, Kastelein J J, Marais A D, Frants R R, Havekes L M
Netherlands Organization for Applied Scientific Research, Institute of Prevention and Health Research, Gaubius Laboratory, Leiden.
J Clin Invest. 1994 Sep;94(3):1252-62. doi: 10.1172/JCI117443.
Genetic and biochemical studies were carried out in 96 relatives of six independently ascertained probands with familial dysbetalipoproteinemia (FD) carrying the APOE2 (Lys146-->Gln) allele. Compared to noncarriers, the 40 heterozygous APOE2 (Lys146-->Gln) allele carriers exhibited markedly increased mean levels of cholesterol and triglyceride in the very low density lipoproteins (VLDL) (1.89 +/- 0.37 vs 0.30 +/- 0.27 and 1.86 +/- 0.37 vs 0.68 +/- 0.27 mmol/liter, respectively) and plasma apolipoprotein (apo) E levels (28.1 +/- 1.6 vs 4.6 +/- 1.1 mg/dl), which is characteristic for FD. By means of a pedigree-based maximum likelihood method we calculated that carrier-status accounted for 57% and 71%, respectively, of the total variance of the ratio (VLDL + IDL)-cholesterol/plasma triglyceride and plasma apoE levels. APOE2 (Lys146-->Gln) and APOE3-Leiden allele carriers were found to differ significantly in: (a) plasma apoE levels, (b) in the amounts of triglycerides in the VLDL and VLDL + IDL fraction, and (c) in the amount of cholesterol in the VLDL and VLDL + IDL fraction relative to the amount of triglyceride in these fractions. In the APOE2 (Lys146-->Gln) allele carriers the VLDL and VLDL + IDL fraction is relatively rich in triglycerides as compared with that in APOE3-Leiden carriers. We hypothesize that these two rare mutations of apoE both lead to dominantly inherited forms of FD along different underlying metabolic defects.
对6个经独立确诊的携带APOE2（Lys146→Gln）等位基因的家族性异常β脂蛋白血症（FD）先证者的96名亲属进行了遗传学和生物化学研究。与非携带者相比，40名杂合APOE2（Lys146→Gln）等位基因携带者的极低密度脂蛋白（VLDL）中胆固醇和甘油三酯的平均水平显著升高（分别为1.89±0.37 vs 0.30±0.27和1.86±0.37 vs 0.68±0.27 mmol/升）以及血浆载脂蛋白（apo）E水平（28.1±1.6 vs 4.6±1.1 mg/dl），这是FD的特征。通过基于家系的最大似然法，我们计算出携带者状态分别占（VLDL + IDL）-胆固醇/血浆甘油三酯比值和血浆apoE水平总方差的57%和71%。发现APOE2（Lys146→Gln）和APOE3-莱顿等位基因携带者在以下方面存在显著差异：（a）血浆apoE水平，（b）VLDL和VLDL + IDL组分中的甘油三酯含量，以及（c）VLDL和VLDL + IDL组分中的胆固醇含量相对于这些组分中甘油三酯含量的比例。与APOE3-莱顿携带者相比，APOE2（Lys146→Gln）等位基因携带者的VLDL和VLDL + IDL组分中甘油三酯相对丰富。我们推测，apoE的这两种罕见突变均沿着不同的潜在代谢缺陷导致FD的显性遗传形式。
