TYPE-III HYPERLIPOPROTEINEMIA ASSOCIATED WITH APOLIPOPROTEIN-E PHENOTYPE-E3/3 - STRUCTURE AND GENETICS OF AN APOLIPOPROTEIN-E3 VARIANT
TYPE-III HYPERLIPOPROTEINEMIA ASSOCIATED WITH APOLIPOPROTEIN-E PHENOTYPE-E3/3 - STRUCTURE AND GENETICS OF AN APOLIPOPROTEIN-E3 VARIANT
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DOI：
10.1172/jci113988
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发表时间：
1989-04-01
影响因子：
15.9
通讯作者：
BERSOT, TP
中科院分区：
文献类型：
--
作者：
RALL, SC;NEWHOUSE, YM;BERSOT, TP
已经描述了一个家系，其中III型高脂蛋白血症与载脂蛋白E表型E3/3相关(Havel，R.J.L.Kotie，J.P.Kane，P.Tun和T.Bersot)。1983年。这位是克莱恩。投资。72：279-387)。在目前的研究中，通过蛋白质和DNA分析确定了该家族先证者的载脂蛋白E的结构。先证者是两个不同的载脂蛋白E等位基因的杂合子，一个编码正常的载脂蛋白E3，另一个编码以前未描述的变异载脂蛋白E3，其中精氨酸取代半胱氨酸在第112位，半胱氨酸取代精氨酸在第142位。对跨越4代的其他9名家庭成员的载脂蛋白E基因分析表明，只有患有III型高脂蛋白血症的5名成员具有载脂蛋白E3变异体。像先证者一样，这五个人都是这个变异的杂合子，这表明这个家族的疾病是以显性方式传播的。变异型载脂蛋白E3与脂蛋白受体的结合能力存在缺陷，这种功能缺陷可能是该家族III型高脂蛋白血症的原因之一。
A family has been described in which type III hyperlipoproteinemia is associated with apo E phenotype E3/3 (Havel, R. J. L. Kotite, J. P. Kane, P. Tun, and T. Bersot. 1983. J., Clin. Invest. 72:279-387). In the current study, the structure of apo E from the propositus of this family was determined using both protein and DNA analyses. The propositus is heterozygous for two different apo E alleles, one coding for normal apo E3 and one for a previously undescribed variant apo E3 in which arginine replaces cysteine at residue 112 and cysteine replaces arginine at residue 142. Apo E gene analysis of nine other family members spanning four generations indicated that only those five members having type III hyperlipoproteinemia possess the variant apo E3. Like the propositus, all five are heterozygous for this variant, suggesting that the disorder in this family is transmitted in a dominant fashion. The variant apo E3 was defective in its ability to bind to lipoprotein receptors, and this functional defect probably contributes to the expression of type III hyperlipoproteinemia in this family.