Kronenberg F, Steinmetz A, Kostner G M, Dieplinger H
Institute of Medical Biology and Human Genetics, University of Innsbruck, Austria.
Crit Rev Clin Lab Sci. 1996;33(6):495-543. doi: 10.3109/10408369609080056.
Lipoprotein(a) [Lp(a)] represents an LDL-like particle to which the Lp(a)-specific apolipoprotein(a) is linked via a disulfide bridge. It has gained considerable interest as a genetically determined risk factor for atherosclerotic vascular disease. Several studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke, and peripheral atherosclerosis. In healthy individuals, Lp(a) plasma concentrations are almost exclusively controlled by the apo(a) gene locus on chromosome 6q2.6-q2.7. More than 30 alleles at this highly polymorphic gene locus determine a size polymorphism of apo(a). There exists an inverse correlation between the size (molecular weight) of apo(a) isoforms and Lp(a) plasma concentrations. The standardization of Lp(a) quantification is still an unresolved task due to the large particle size of Lp(a), the presence of two different apoproteins [apoB and apo(a)], and the large size polymorphism of apo(a) and its homology with plasminogen. A working group sponsored by the IFCC is currently establishing a stable reference standard for Lp(a) as well as a reference method for quantitative analysis. Aside from genetic reasons, abnormal Lp(a) plasma concentrations are observed as secondary to various diseases. Lp(a) plasma levels are elevated over controls in patients with nephrotic syndrome and patients with end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus result mainly from insufficient sample sizes of numerous studies. Large studies and those including apo(a) phenotype analysis came to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In noninsulin-dependent diabetics, Lp(a) is not elevated. Conflicting data also exist from studies in patients with familial hypercholesterolemia. Several case-control studies reported elevated Lp(a) levels in those patients, suggesting a role of the LDL-receptor pathway for degradation of Lp(a). However, recent turnover studies rejected that concept. Moreover, family studies also revealed data arguing against an influence of the LDL receptor for Lp(a) concentrations. Several rare diseases or disorders, such as LCAT- and LPL-deficiency as well as liver diseases, are associated with low plasma levels or lack of Lp(a).
脂蛋白(a)[Lp(a)]是一种类似低密度脂蛋白（LDL）的颗粒，Lp(a)特异性载脂蛋白(a)通过二硫键与之相连。作为动脉粥样硬化性血管疾病的一种遗传决定风险因素，它已引起了相当大的关注。多项研究描述了血浆Lp(a)水平升高与冠心病、中风和外周动脉粥样硬化之间的相关性。在健康个体中，血浆Lp(a)浓度几乎完全由位于6号染色体q2.6-q2.7上的载脂蛋白(a)基因位点控制。该高度多态性基因位点上的30多个等位基因决定了载脂蛋白(a)的大小多态性。载脂蛋白(a)异构体的大小（分子量）与血浆Lp(a)浓度呈负相关。由于Lp(a)颗粒尺寸大、存在两种不同的载脂蛋白[载脂蛋白B和载脂蛋白(a)]、载脂蛋白(a)的大小多态性大及其与纤溶酶原的同源性，Lp(a)定量的标准化仍是一项未解决的任务。由国际临床化学和检验医学联合会（IFCC）赞助的一个工作组目前正在建立Lp(a)的稳定参考标准以及定量分析的参考方法。除了遗传原因外，在各种疾病继发情况下也可观察到血浆Lp(a)浓度异常。肾病综合征患者和终末期肾病患者的血浆Lp(a)水平高于对照组。肾移植后，Lp(a)浓度降至与载脂蛋白(a)类型匹配的对照组所观察到的值。关于糖尿病患者Lp(a)的有争议数据主要源于众多研究样本量不足。大型研究以及包括载脂蛋白(a)表型分析的研究得出结论，胰岛素依赖型患者的Lp(a)水平未升高或仅中度升高。在非胰岛素依赖型糖尿病患者中，Lp(a)未升高。关于家族性高胆固醇血症患者的研究也存在相互矛盾的数据。几项病例对照研究报告这些患者的Lp(a)水平升高，提示LDL受体途径在Lp(a)降解中起作用。然而，最近的周转率研究否定了这一概念。此外，家族研究也揭示了一些数据，反对LDL受体对Lp(a)浓度有影响。几种罕见疾病或病症，如卵磷脂胆固醇酰基转移酶（LCAT）和脂蛋白脂肪酶（LPL）缺乏症以及肝脏疾病，与血浆Lp(a)水平低或缺乏Lp(a)有关。
