Most ApoL1 Is Secreted by the Liver
Most ApoL1 Is Secreted by the Liver
复制标题
DOI：
10.1681/asn.2016040441
复制
发表时间：
2017-04-01
影响因子：
13.6
通讯作者：
Berg, Anders H.
中科院分区：
文献类型：
--
作者：
Shukha, Khuloud;Mueller, Jessica L.;Berg, Anders H.
APOL1基因中的两个编码序列变体（G1和G2）解释了最近非洲血统人群中FSGS，HIV相关肾病和高血压归因的ESRD风险增加的大部分原因。ApoL 1蛋白在多种细胞组织中表达。已经假设大部分循环ApoL1是由肝脏产生的，但这尚未得到证实。使用质谱法，我们对两名肝移植受者的循环ApoL1进行基因分型和定量，这两名肝移植受者的原生ApoL1基因型与已故供体的基因型不同，这使我们能够区分肝脏和非肝脏产生的ApoL1。我们的研究结果证实，肝脏确实是循环ApoL1的主要来源。然而，肝脏并不是循环ApoL1的唯一来源，因为我们发现即使在肝脏移植后，残留量的天然ApoL1仍继续在血液中循环。
Two coding sequence variants in the APOL1 gene (G1 and G2) explain much of the increased risk for FSGS, HIV-associated nephropathy, and hypertension-attributed ESRD among people of recent African ancestry. The ApoL1 protein is expressed in a wide variety of cell tissues. It has been assumed that the majority of circulating ApoL1 is produced by the liver, but this has not been shown. Using mass spectrometry, we genotyped and quantified the circulating ApoL1 in two liver transplant recipients whose native APOL1 genotype differed from the genotype of the deceased donors, allowing us to differentiate liver-from nonliver-produced ApoL1. Our findings confirm that the liver is indeed the main source of circulating ApoL1. However, the liver is not the sole source of circulating ApoL1, because we found that residual amounts of native ApoL1 continued to circulate in the blood, even after the liver transplant.