Apolipoprotein E1 Baden (Arg180→Cys) -: A new apolipoprotein E variant associated with hypertriglyceridemia
Apolipoprotein E1 Baden (Arg180→Cys) -: A new apolipoprotein E variant associated with hypertriglyceridemia
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DOI：
10.1016/s0009-8981(00)00372-7
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发表时间：
2001-01-01
影响因子：
5
通讯作者：
März, W
中科院分区：
文献类型：
--
作者：
Hoffmann, MM;Scharnagl, H;März, W
载脂蛋白E介导乳糜微粒和极低密度脂蛋白残留物从血浆中清除。它在序列上具有多态性，并且三个常见等位基因（epsilon 2、epsilon 3、epsilon 4）的产物在与脂蛋白受体的结合方面彼此不同。ApoE 2在结合方面有缺陷，并且apoE 2的纯合性与III型高脂蛋白血症（HLP）相关。已发现apoE的其他罕见亚型与显性III型HLP或高脂血症的发生相关。我们确定了一个42岁的高脂血症妇女与apoE表型3/1。使用Afl III/Hae II的限制性同种型导致明显的apoE基因型3/2，表明突变发生在ε 2等位基因中。DNA序列分析显示成熟apoE的第180位氨基酸残基密码子的第一位存在C->T点突变。这预测了ARG（180）->Cys的变化。突变改变了核酸内切酶HaeII的识别位点，这使我们能够快速筛选这种突变。在先证者的亲属中，apoE 1 Baden与高脂血症一致相关。类似于与高甘油三酯血症相关的其他apoE变体，Arg（180）->Cys突变位于apoE的脂质结合结构域内。因此，我们认为，apoE 1巴登可能会导致hypertrigylceridemia，可能是通过抑制与极低密度脂蛋白相关的甘油三酯的水解。(C)2001爱思唯尔科技有限公司。保留所有权利。
Apolipoprotein (apo) E mediates the removal of chylomicron and very low density lipoprotein remnants from plasma. It is polymorphic in sequence and the products of the three common alleles (epsilon2, epsilon3, epsilon4) differ from one another in their binding to lipoprotein receptors. ApoE2 is defective in binding and homozygosity for apoE2 is associated with type III hyperlipoproteinemia (HLP). Other rare isoforms of apoE have been found to be associated either with dominant type III HLP or with the development of hypertriglyceridemia. We identified a 42 year-old hypertriglyceridemic woman with an apoE phenotype 3/1. Restriction isotyping using AflIII/HaeII resulted in an apparent apoE genotype 3/2, suggesting that the mutation occurred in an epsilon2 allele. DNA sequence analysis revealed a C-->T point mutation at the first position of the codon for amino acid residue 180 of the mature apoE. This predicted a change ARG(180)-->Cys. The mutation altered a recognition site for the endonuclease HaeII, which allowed us rapidly to screen for this mutation. In relatives of the proband, apoE1 Baden was consistently associated with hypertriglyceridemia. Similar to other apoE variants linked to hypertriglyeridemia, the Arg(180)-->Cys mutation is located within the lipid binding domain of apoE. We therefore suggest that apoE1 Baden may cause hypertrigylceridemia, possibly by inhibiting the hydrolysis of triglycerides associated with very low density lipoproteins. (C) 2001 Elsevier Science B.V. All rights reserved.