Coding, modifier, and regulatory effects shape circulating APOL1 levels

Walt E. Adamson

doi:10.1093/hmg/ddag087

2026-09-18

DOI：10.1093/hmg/ddag087

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摘要

En 中文

APOL1变异体G1和G2是近期撒哈拉以南非洲血统人群慢性肾脏病的主要遗传风险因素，但基因型与疾病之间的机制仍不明确。循环APOL1可能发挥关键作用，但特定基因型和调控变异如何影响循环APOL1水平尚不完全清楚。我们分析了来自43,587名英国生物银行参与者的Olink测量的APOL1 NPX（标准化蛋白质表达水平）。在近期撒哈拉以南非洲血统个体中，评估了APOL1 NPX与已知基因型的关联，包括对G1、G2、E150K（rs2239785）和N264K（rs73885316）的分析。我们还研究了APOL1位点的蛋白质数量性状位点（pQTL）和顺式作用变异，包括预测的微小RNA结合位点。结果表明，APOL1 NPX以APOL1基因型依赖的方式变化。E150K、G1和G2与APOL1 NPX表现出明显的剂量依赖关系，其中G2效应最大。在考虑APOL1基因型后，自报黑人或黑人英国族裔个体的APOL1 NPX仍较高，这与额外的调控元件一致。多个位于APOL1附近的顺式调控变异独立与APOL1 NPX相关，可能有助于解释与血统相关的差异。这些发现共同表明，APOL1基因型是APOL1 NPX的主要决定因素，且G1和G2具有不同的生物学效应。调控变异为APOL1 NPX的控制增加了另一层机制，可能有助于解释群体差异。这些发现为理解APOL1变异的基因型特异性分子效应提供了生物学框架。

期刊

Human Molecular Genetics

IF:

3.2

论文数:

1.1W

被引数:

3.5W

机构

University of Liverpool

学者数:

478

论文数: 227

被引数: 0

university of glasgow

学者数:

569

论文数: 264

被引数: 0

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