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以色列透析人群中G1和G2变体的多民族患病率。

Multiethnic prevalence of the G1 and G2 variants among the Israeli dialysis population.

作者信息

Ben-Ruby Dror, Atias-Varon Danit, Kagan Maayan, Chowers Guy, Shlomovitz Omer, Slabodnik-Kaner Keren, Mano Neta, Avayou Shany, Atsmony Yariv, Levin Dana, Dotan Edo, Calderon-Margalit Ronit, Shnaider Alla, Haviv Yosef S, Birk Ohad S, Hadar Noam, Anikster Yair, Berar Yanay Noa, Chernin Gil, Kruzel-Davila Etty, Beckerman Pazit, Rozen-Zvi Benaya, Doctor Gabriel T, Stanescu Horia C, Shemer Revital, Pras Elon, Reznik-Wolf Haike, Nahum Ayelet Hashahar, Dominissini Dan, Skorecki Karl, Vivante Asaf

机构信息

Genetic Kidney Disease Research Laboratory, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.

Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel.

出版信息

Clin Kidney J. 2024 Dec 6;18(2):sfae397. doi: 10.1093/ckj/sfae397. eCollection 2025 Feb.

Abstract

BACKGROUND AND HYPOTHESIS

The two apolipoprotein L1 () variants, G1 and G2, are common in populations of sub-Saharan African ancestry. Individuals with two of these alleles (G1 or G2) have an increased risk for a spectrum of non-diabetic chronic kidney diseases. However, these variants are typically not observed outside of populations that self-identify as current continental Africans or having clear recent African ancestry such as, most notably, African Americans, and other large population groups in the Americas and several European countries. We hypothesized that the diverse ethnic groups within the Israeli population may exhibit varying levels of recent African ancestry. Therefore, it is plausible that risk alleles might be present even in individuals who do not self-identify as being of sub-Saharan African descent.

METHODS

We non-selectively screened people with kidney failure across Israel for risk variants using restriction fragment length polymorphism.

RESULTS

We recruited 1744 individuals from 38 dialysis units in Israel. We identified eight patients of Moroccan Jewish, Bedouin, or Muslim Arab ancestry, who carry at least one G1 or G2 allele. None of the eight patients carried the protective p.N264K variant. Furthermore, despite all Bedouin individuals being G2 heterozygous, the G2 minor allele frequency was significantly enriched in kidney failure cases compared to ethnically matched controls ( = .006).

CONCLUSIONS

These findings show that G1 and G2 allelic variants are present in populations previously not appreciated to possess recent sub-Saharan ancestry and suggest that a single G2 risk variant may confer increased risk for chronic kidney disease in certain population contexts.

摘要

背景与假设

载脂蛋白L1(APOL1)的两种变体G1和G2在撒哈拉以南非洲血统人群中很常见。携带其中两个等位基因(G1或G2)的个体患一系列非糖尿病慢性肾脏病的风险增加。然而,这些变体通常在自我认定为当前非洲大陆人或有明确近期非洲血统的人群之外未被观察到,最显著的是非洲裔美国人,以及美洲和几个欧洲国家的其他大型人群。我们假设以色列人群中的不同种族群体可能表现出不同程度的近期非洲血统。因此,即使在不自我认定为撒哈拉以南非洲血统的个体中也可能存在APOL1风险等位基因,这是合理的。

方法

我们使用限制性片段长度多态性对以色列各地的肾衰竭患者进行非选择性筛查,以检测APOL1风险变体。

结果

我们从以色列的38个透析单位招募了1744名个体。我们鉴定出8名具有摩洛哥犹太、贝都因或穆斯林阿拉伯血统的患者,他们携带至少一个G1或G2等位基因。这8名患者均未携带保护性的APOL1 p.N264K变体。此外,尽管所有贝都因个体都是G2杂合子,但与种族匹配的对照组相比,肾衰竭病例中G2次要等位基因频率显著富集(P = 0.006)。

结论

这些发现表明,APOL1 G1和G2等位基因变体存在于以前未被认为具有近期撒哈拉以南血统的人群中,并表明单一的G2风险变体可能在某些人群背景下增加慢性肾脏病的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/064a/11803305/f8d629c186c0/sfae397fig1g.jpg

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