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

载脂蛋白E表型测定对家族性高胆固醇血症患者的风险研究

• 批准号: 07670845
• 负责人: ASAMI Tadashi
• 金额: $ 1.54万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670845/
• 关键词: familial hypercholesterolemia; apolipoprotein E; phenotype; アポE; フェノタイピング

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.

在家族性高胆固醇血症(FH)中，血清总胆固醇(TC)水平的个体间变异性增加了一种可能性，即除低密度脂蛋白受体外，一些尚不清楚的因素也可能对其起作用。载脂蛋白E(ApoE)是一种参与胆固醇转运和代谢的血浆蛋白。载脂蛋白E基因的等位基因变异(E_2/2、E_2/3、E_2/4、E_3/3、E_4/3、E_4/4)在此背景下，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、机会蛋白尿和/或血尿、肾脏疾病)中，apoE表型如下；E3/3(192，71.6%)，E4/3(45，16.8%)，E3/2(24，9.0%)，E5/3(5，1.9%)，以及罕见的变异型E7/4。143例正常人apoE表型分别为E3/3(100，70.0%)，E4/3(29，20.4%)，E3/2(10，7.0%)，E4/2和E5/3(4，2.8%)。FH患儿与正常儿童比较，apoE各表型分布差异无统计学意义。无E4等位基因的FH儿童对降胆固醇治疗有反应的倾向。此外，至少有一个E4等位基因的肥胖儿童血清载脂蛋白B水平更高，这表明未来发生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表现出更强的类固醇抵抗能力。

项目成果

Asami T, et al.: "Two families of Lowe oculocerebrorenal syndrom with elevated serum HDL cholesterol levels and CETP gene mutation." Acta Paed Int J Paed. 86・1. 41-45 (1997)

Asami T 等：“血清 HDL 胆固醇水平升高和 CETP 基因突变的 Lowe 眼脑肾综合征的两个家族。”Acta Paed Int J Paed 86·1 (1997)。

Asami T, Gomi T, et al: "Persistent non-familial asymptomatic hyperphosphatasemia:a report on three cases." Acta Paediatrica Int J Pead. 84. 346-348 (1995)

Asami T、Gomi T 等人：“持续性非家族性无症状高磷酸酶血症：三例报告”。

Asami T, et al.: "Incidence of febrile convusions in children with congenital hypothyroidism." Acta Paed. (印刷中). (1998)

Asami T 等人：“先天性甲状腺功能减退症儿童的发热性惊厥的发生率”（Acta Paed）（1998 年）。

Asami T, Kikuchi T, et al: "Effects of L-thyroxine on serum lipid profiles in infants with congenital hypothyroidism." J Pediatr. 127. 812-814 (1995)

Asami T、Kikuchi T 等人：“L-甲状腺素对先天性甲状腺功能减退症婴儿血清脂质谱的影响”。

Asami T,et al.: "Cholesterol levels in children with renal diseases." Pediatiric Nephrology. (in press).

Asami T 等人：“肾病儿童的胆固醇水平。”