Study on the risk of patiens with familial hypercholesterolemia by the determination of apolipoprotein E phenotyping

在家族性高胆固醇血症（FH）中，血清总胆固醇（TC）水平的个体间差异提出了一种可能性，即除LDL受体外，一些未知因素也可能导致高胆固醇血症。载脂蛋白E （apoE）是一种参与胆固醇转运和代谢的血浆蛋白。apoE基因的等位基因变异（E2/2、E2/3、E2/4、E3/3、E4/3和E4/4）是造成血清TC个体间变异的一部分原因。考虑到这一背景，我们研究了FH儿童apoE表型与血清TC水平的关系。在269例儿童患者（高胆固醇血症、甲状腺功能减退、恶性疾病、偶发蛋白尿和/或血尿、肾脏疾病）中，载脂蛋白e表型如下；E3/3 (192 71.6%), E4/3(45岁,16.8%),E3/2(24岁,9.0%),E5/3(5 1.9%),和一个非常罕见的变异E7/4。143例正常对照的apoE表型为E3/3 (100,70.0%)；E4/3(29岁,20.4%);E3/2 (10,7.0%)；E4/2和E5/3（4.2.8%）。与正常儿童相比，FH患儿各apoE表型分布无显著差异。无E4等位基因的FH患儿有降低胆固醇治疗的倾向。此外，至少有一个E4等位基因的肥胖儿童血清载脂蛋白水平更高，表明未来冠状动脉粥样硬化的风险更高，而至少有一个E4等位基因的肾病儿童显示出更强的类固醇抗性。

In familial hypercholelsterolemia (FH), the inter-individual variability in serum total cholesterol (TC) kevels raises a possibility that some still unknown factors, other than LDL receptors, may also contribute to them. Apolipoprotein E (apoE) is a plasma protein involved in cholesterol transport and metaboslim. The allelic variation in the apoE gene (E2/2, E2/3, E2/4, E3/3, E4/3, and E4/4.) is responsible for a proportion of the inter-individual variability in serum TC.With this background in mind, we investigated the association of apoE phenotypes with serum TC levels in FH children.In 269 pediatric patients (hypercholesterolemia, hypothyroidism, malignant diseases, chance proteinuria and/or hematuria, renal diseases), apoE phenotypes were as follows ; E3/3 (192,71.6%), E4/3 (45,16.8%), E3/2 (24,9.0%), E5/3 (5,1.9%), and a very rare variant E7/4.The apoE phenotype of the 143 normal control subjects was E3/3 (100,70.0%) ; E4/3(29,20.4%) ; E3/2 (10,7.0%) ; and E4/2 and E5/3 (4,2.8%). Children with FH had no significant differences in each apoE phenotype distribution as comapared with the normal children. FH children without E4 allele had a tendency to respond cholesterol lowering therapy. In addition, obese children, with at least one E4 allele, had higher serum apoB levels, suggesting higher risk for future coronary atherosclerosis, and nephrotic children with at least one E4 allele were shown to be more steroid resistant.