Kronenberg Florian
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Schöpfstr. 41, 6020 Innsbruck, Austria.
Curr Opin Lipidol. 2017 Feb;28(1):39-45. doi: 10.1097/MOL.0000000000000371.
Chronic kidney disease (CKD) is a common disease with an estimated prevalence of 10-12%. There are pronounced differences between ethnicities with a 3-fold to 4-fold higher lifetime risk for end-stage kidney disease in African Americans compared to European Americans. The purpose of this review was to discuss recent findings on two apolipoproteins (apolipoprotein L1 and A-IV) in the context of kidney disease and kidney function.
The observation that certain apolipoprotein L1 risk genotypes that are only present in African Americans might explain a major fraction of the ethnic differences for nondiabetic CKD has set the stage for this otherwise under-researched apolipoprotein. These risk genotypes on the one hand protect African Americans against African sleeping sickness but cause on the other hand several types of nondiabetic CKD. We are currently beginning to understand the mechanisms how apolipoprotein L1 is involved in the modification of lysosomal and cytoplasmic membranes. The second protein, apolipoprotein A-IV (apoA-IV), turned out to be an early marker of kidney impairment not only in patients with primary CKD but also in individuals from the general population. Genetic studies provided strong support of a causal effect of kidney function on apoA-IV concentrations.
These two apolipoproteins have very distinct properties. Apolipoprotein L1 is causally involved in the development of nondiabetic CKD in African Americans. In contrast, apoA-IV is an early marker for kidney impairment.
慢性肾脏病(CKD)是一种常见疾病,估计患病率为10% - 12%。不同种族之间存在显著差异,与欧洲裔美国人相比,非裔美国人终末期肾病的终生风险高3至4倍。本综述的目的是在肾脏疾病和肾功能的背景下讨论两种载脂蛋白(载脂蛋白L1和A-IV)的最新研究结果。
某些仅在非裔美国人中存在的载脂蛋白L1风险基因型可能解释了非糖尿病性CKD种族差异的很大一部分,这一发现为这种此前研究较少的载脂蛋白奠定了研究基础。这些风险基因型一方面保护非裔美国人免受非洲昏睡病的侵害,但另一方面会导致几种类型的非糖尿病性CKD。我们目前开始了解载脂蛋白L1参与溶酶体和细胞质膜修饰的机制。第二种蛋白质,载脂蛋白A-IV(apoA-IV),不仅在原发性CKD患者中,而且在普通人群中,都是肾脏损害的早期标志物。遗传学研究有力支持了肾功能对apoA-IV浓度的因果效应。
这两种载脂蛋白具有非常不同的特性。载脂蛋白L1在非裔美国人非糖尿病性CKD的发生中起因果作用。相比之下,apoA-IV是肾脏损害的早期标志物。