Identification of a founder haplotype of APOE Kyoto variant in lipoprotein glomerulopathy.

IF 4.6 2区医学 Q1 UROLOGY & NEPHROLOGY

Clinical Kidney Journal Pub Date : 2025-07-21 eCollection Date: 2025-08-01 DOI:10.1093/ckj/sfaf234

Hongyan Wu, Zhaoxia He, Jing Yang, Yi Zhou, Zhi Yang, Zhangxue Hu, Yuan Yang

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引用次数: 0

Abstract

Background: Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant inherited kidney disease with incomplete penetrance, characterized by nephrotic-range proteinuria, hypertriglyceridemia and progressive renal dysfunction with elevated serum apoE level. More than 15 APOE mutations have been associated with LPG, with APOE Kyoto (Arg43Cys) the leading mutation in about 200 patients. We previously observed clustering of "APOE Kyoto causing LPG" in a Han population in China. We now explore the haplotype of the APOE Kyoto heterozygotes and the distribution of LPG patients in China.

Methods: A total of 115 APOE Kyoto heterozygotes were enrolled and identified by Sanger sequencing, and in this study, the haplotypes of Kyoto and counterpart alleles were investigated by TA cloning and Sanger sequencing.

Results: Overall, 114 out of 115 APOE Kyoto alleles shared an identical haplotype, likely from haplotype 1 in ε3. Among heterozygotes, the counterpart of APOE Kyoto allele showed haplotype diversity, and the difference in haplotype distribution of the counterpart allele was not observed between LPG patients and asymptomatic carriers.

Conclusions: This study provides further evidence for the founder effect of APOE Kyoto may play a critical role in the progression of LPG.

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脂蛋白肾小球病APOE京都变异创始单倍型的鉴定。

背景：脂蛋白肾小球病（LPG）是一种罕见的常染色体显性遗传病，具有不完全外显性，以肾范围蛋白尿、高甘油三酯血症和进行性肾功能障碍为特征，并伴有血清载脂蛋白e水平升高。超过15种APOE突变与LPG相关，其中APOE Kyoto （Arg43Cys）是约200例患者的主要突变。我们之前在中国汉族人群中观察到“APOE京都引起LPG”的聚集性。我们现在探讨APOE京都杂合子的单倍型和LPG患者在中国的分布。方法：采用Sanger测序法对115个APOE Kyoto杂合子进行登记和鉴定，采用TA克隆和Sanger测序法对Kyoto及其对应等位基因的单倍型进行研究。结果：总体而言，115个APOE京都等位基因中有114个具有相同的单倍型，可能来自ε3的单倍型1。在杂合子中，APOE京都等位基因的对应物呈现单倍型多样性，LPG患者与无症状携带者之间对应物的单倍型分布未见差异。结论：本研究进一步证明APOE京都的奠基者效应可能在LPG的进展中起关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Kidney Journal Medicine-Transplantation

CiteScore

6.70

自引率

10.90%

发文量

242

审稿时长

8 weeks

期刊介绍： About the Journal Clinical Kidney Journal: Clinical and Translational Nephrology (ckj), an official journal of the ERA-EDTA (European Renal Association-European Dialysis and Transplant Association), is a fully open access, online only journal publishing bimonthly. The journal is an essential educational and training resource integrating clinical, translational and educational research into clinical practice. ckj aims to contribute to a translational research culture among nephrologists and kidney pathologists that helps close the gap between basic researchers and practicing clinicians and promote sorely needed innovation in the Nephrology field. All research articles in this journal have undergone peer review.