Molecular cloning and characteristics of a new apolipoprotein C-II mutant identified in three unrelated individuals with hypercholesterolemia and hypertriglyceridemia.
Molecular cloning and characteristics of a new apolipoprotein C-II mutant identified in three unrelated individuals with hypercholesterolemia and hypertriglyceridemia.
复制标题
在三个不相关的高胆固醇血症和高甘油三酯血症个体中鉴定出新的载脂蛋白 C-II 突变体的分子克隆和特征。
DOI：
10.1093/hmg/2.1.69
复制
发表时间：
1993
影响因子：
3.5
通讯作者：
Kane,JP
中科院分区：
文献类型：
--
作者：
Pullinger,CR;Zysow,BR;Hennessy,LK;Frost,PH;Malloy,MJ;Kane,JP
在三名不相关的高脂血症患者中发现了载脂蛋白 C-II (apoC-II) 的一种新的罕见突变形式，命名为 apoC-IISF。第一个是白人男性，总胆固醇 (TC) 为 313 mg/dl，总甘油三酯 (TG) 为 282 mg/dl；第二个是非洲裔美国女性（TC 345 mg/dl，TG 203 mg/dl）；第三个是非洲裔美国男性（TC 345 mg/dl，TG 1000 mg/dl）。发现每个受试者都是杂合子，密码子中残基 38 的 G 替换为 A，导致 Lys 替换为 Glu。这就是 pl 值增加到 5.3 的原因。第三名患者除了 apoC-IISF 之外，还患有另一种电荷变异体 apoC-II2。这是通过 DNA 测序确定的，证实了之前通过本实验室肽片段分析预测的残基 55 处的谷氨酰胺 (Gln) 与赖氨酸 (Lys) 的变化。当将apoC-IISF激活脂蛋白脂肪酶的能力与正常apoC-II进行比较时，观察到类似的米氏激活常数和激活能。这表明残基 38 周围电荷的主要变化对活化性能没有影响。该变体可能在其他一些特性上发生改变，例如脂质结合，但由于 apoC-IISF 的分布表明与脂质水平不存在简单的共同遗传，因此尚不清楚它在观察到的高脂血症中发挥的作用有多大。与变体一起作用的其他因素的存在可能导致血脂水平升高。
A new rare mutant form of apolipoprotein C-II (apoC-II), designated apoC-IISF, was identified in three unrelated hyperlipidemic patients. The first was a Caucasian male with a total cholesterol (TC) of 313 mg/dl and total triglyceride (TG) of 282 mg/dl, the second an African-American female (TC 345 mg/dl, TG 203 mg/dl) and the third, an African—American male (TC 345 mg/dl, TG 1000 mg/dl). Each subject was found to be heterozygous for a G to A substitution in the codon for residue 38, resulting in a Lys for Glu exchange. This accounts for the increased pl value of 5.3. The third patient, in addition to apoC-IISF, had apoC-II2, another charge variant. This was determined by DNA sequencing, confirming the Gln for Lys change at residue 55 previously predicted by analysis of peptide fragments in this laboratory. Similar Michaelis constants of activation and activation energies were observed when the ability of apoC-IISFto activate lipoprotein lipase was compared to normal apoC-II. This indicates that major changes in charge around residue 38 lack effect on the activation properties. The variant may be altered in some other property, such as lipid binding, but since the distribution of apoC-IISFrevealed no simple co-inheritance with lipid levels, it is unclear to what extent it plays a role in the observed hyperlipidemia. The presence of other factors acting together with the variant may predispose to elevated lipid levels.