载脂蛋白E R112;R251G:一种在高脂血症和冠心病患者中发现的羧基末端变异

Amrit K Kang , David J.A Jenkins , Thomas M.S Wolever , Murray W Huff , Graham F Maguire , Philip W Connelly , Robert A Hegele
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引用次数: 3

摘要

一名49岁的高胆固醇血症男性,在运动测试中发现心电图ST段明显下降,通过等电聚焦发现APOE E3/3表型,但通过HhaI限制等型发现APOE E3/3基因型。先证者APOE基因序列分析发现密码子251处G→C点突变。这预测了密码子251编码的氨基酸从精氨酸到甘氨酸的变化。突变发生在编码112位精氨酸的等位基因上,该变异被命名为APOE R112;R251G。R251G的改变改变了内切酶StuI的识别位点,是快速筛选该突变的限制性内切同型方法的基础。在先证者亲属中,APOE R112;R251G在高脂血症和动脉粥样硬化患者中均存在。Apo E R112;r251g -含极低密度脂蛋白,与巨噬细胞正常结合。然而,先证者对膳食脂肪挑战有异常的餐后脂蛋白反应。APOE R112的关联;表型异常的R251G提示羧基末端的氨基酸变化,可能与密码子112处常见的氨基酸多态性相结合,对该家族成员的脂蛋白代谢有功能影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients with hyperlipidemia and coronary heart disease

A 49 year-old hypercholesterolemic male with marked electrocardiographic ST segment depression on exercise testing was found to have an apo E E3/3 phenotype by isoelectric focusing, but an APOE E4/3 genotype using HhaI restriction isotyping. DNA sequence analysis of the proband's APOE gene found a G→C point mutation at codon 251. This predicted a change in the amino acid encoded by codon 251, from arginine to glycine. The mutation occurred on an allele that encoded arginine at position 112 and this variant was named APOE R112; R251G. The R251G change altered a recognition site for the endonuclease StuI and was the basis for a restriction isotyping method to rapidly screen for this mutation. In relatives of the proband, APOE R112; R251G was consistently found in subjects with both hyperlipidemia and atherosclerosis. Apo E R112; R251G-containing very low density lipoproteins bound normally to macrophages in vitro. However, the proband had an abnormal post-prandial lipoprotein response to a dietary fat challenge. The association of APOE R112; R251G with abnormal phenotypes suggests that the amino acid change in the carboxy-terminal, perhaps in combination with the common amino acid polymorphism at codon 112, has a functional impact upon lipoprotein metabolism in members of this family.

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