HDL STRUCTURE AND METABOLISM IN A WOMEN WITH LOW HDL

高密度脂蛋白(高密度脂蛋白)在预防疾病中的重要性 动脉粥样硬化的发展已经得到了很好的证实。而当 高密度脂蛋白预防动脉粥样硬化形成的机制被推测 作为它的次要角色，S在胆固醇反向运输中的作用 该功能的结构要求是不确定的。遗传 导致异常高密度脂蛋白颗粒的紊乱可能会揭示这一点 问题。 我们已经确认了一名48岁的女性，在 0-13 mg/dl范围。使用聚合酶链式反应，我们有 初步确定了她载脂蛋白A-I基因的突变。令人惊讶的是， 尽管她的高密度脂蛋白胆固醇水平极低，但她没有证据表明 CAD。该假定突变与高密度脂蛋白相关性的探讨 功能可能阐明A-I脱辅基蛋白的某些方面 结构/功能关系，并有助于理解 高密度脂蛋白对冠心病的保护作用。 我们计划通过以下方式研究先证者的高密度脂蛋白颗粒结构 免疫亲和柱层析、十二烷基硫酸钠-聚丙烯酰胺凝胶 电泳法和非变性梯度聚丙烯酰胺凝胶 电泳法。载脂蛋白A-I结构将通过两个维度进行评估 凝胶电泳法。载脂蛋白A-I基因将用技术进行评估 包括聚合酶链式反应，Southern杂交，创造和 筛选基因组DNA文库，DNA测序。载脂蛋白的代谢 A-I将通过三氢化氢的内源性标记方案进行研究 亮氨酸作为示踪剂。

The importance of high density lipoproteins (HDL) in protecting against the development of atherosclerosis has been well established. While the mechanism by which HDL protects against atheroma formation is presumed to be secondary to it' s role in reverse cholesterol transport, the structural requirements for that function are uncertain. Genetic disorders resulting in abnormal HDL particles may shed light on this question. We have identified a 48 year old woman with HDL cholesterol levels in the 0-13 mg/dl range. Using the polymerase chain reaction, we have tentatively identified a mutation in her apo A-I gene. Surprisingly, despite her extremely low HDL cholesterol levels, she has no evidence of CAD. The exploration of the relevance of this putative mutation to HDL function may illuminate aspects of the A-I apoprotein's structure/function relationships, and aid in the understanding of the protective effect of HDL against coronary artery disease. We plan to investigate HDL particle structure in the proband by immunoaffinity column chromatography, SDS polyacrylamide gel electrophoresis, and non-denaturing gradient polyacrylamide gel electrophoresis. Apo A-I structure will be assessed by two dimensional gel electrophoresis. The apo A-I gene will be assessed with techniques including the polymerase chain reaction, Southern blotting, creating and screening a genomic DNA library, and DNA sequencing. Metabolism of apo A-I will be studied by an endogenous labeling protocol with trideuterated leucine as the tracer.