APOL1 Risk Genotypes Are Associated With Early Kidney Damage in Children in Sub-Saharan Africa
APOL1 Risk Genotypes Are Associated With Early Kidney Damage in Children in Sub-Saharan Africa
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DOI：
10.1016/j.ekir.2019.04.002
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发表时间：
2019-07-01
影响因子：
6
通讯作者：
Levtchenko, Elena N.
中科院分区：
文献类型：
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作者：
Ekulu, Pepe M.;Nkoy, Agathe B.;Levtchenko, Elena N.
前言：载脂蛋白-L1(APOL1)风险变异体G1和G2增加了非裔美国人患慢性肾脏疾病(CKD)的风险，包括与HIV相关的CKD。然而，来自生活在非洲的人口，特别是儿童的此类数据仍然有限。我们的研究旨在确定APOL1风险变异在普通儿科人群和HIV感染儿童中的患病率，并评估这些变异与早期CKD的相关性。方法：在一项横断面研究中，我们在刚果民主共和国金沙萨招募了412名普通人群和401名HIV感染儿童。APOL1高危基因(HRG)定义为2个风险变异(G1/G1、G2/G2或G1/G2)，低危基因(LRG)定义为0或1个风险变异。结果：APOL1序列分析显示，412名受试者中有29名(7.0%)携带HRG，84名(20.4%)携带G1/G0型，61名(14.8%)携带G2/G0型。在感染艾滋病毒的儿童中，401人中有23人(5.7%)携带HRG，在LRG的流行率方面观察到与普通人群相同的趋势。单因素分析显示，在普通人群中，29名HRG携带者中有5名(17.2%)蛋白尿升高，而383名LRG携带者中有35名(9.0%)(优势比[OR]2.1，95%可信区间[CI]0.6~6.0；P=0.13)。在HIV感染的儿童中，携带APOL1 HRG的参与者发生蛋白尿的几率几乎是携带LRG的儿童的22倍。结论：APOL1风险变异在刚果民主共和国儿童中普遍存在。HRG携带者增加了早期肾脏疾病的几率，感染艾滋病毒显著增加了这种几率。
Introduction: Apolipoprotein-L1 (APOL1) risk variants G1 and G2 increase the risk of chronic kidney disease (CKD), including HIV-related CKD, among African Americans. However, such data from populations living in Africa, especially children, remain limited. Our research aimed to determine the prevalence of APOL1 risk variants and to assess the association between these variants and early-stage CKD in the general pediatric population and HIV-infected children.Methods: In a cross-sectional study, we enrolled 412 children from the general population and 401 HIV-infected children in Kinshasa, Democratic Republic of Congo (DRC). APOL1 high-risk genotype (HRG) was defined by the presence of 2 risk variants (G1/G1, G2/G2, or G1/G2), and low-risk genotype (LRG) by the presence of 0 or 1 risk variants. The main outcome was elevated albuminuria, defined as a urinary albumin/creatinine ratio >= 30 mg/g.Results: APOL1 sequence analysis revealed that in the general population, 29 of 412 participants (7.0%) carried HRG, 84 of 412 (20.4%) carried the G1/G0 genotype, and 61 of 412 (14.8%) carried the G2/G0 genotype. In HIV-infected children, 23 of 401 (5.7%) carried HRG, and the same trend as in the general population was observed in regard to the prevalence of LRG. Univariate analysis showed that in the general population, 5 of 29 participants (17.2%) carrying HRG had elevated albuminuria, compared with 35 of 383 (9.0%) with LRG (odds ratio [OR] 2.1, 95% confidence interval [CI] 0.6-6.0; P = 0.13). In HIV-infected children, participants who carried APOL1 HRG had almost 22-fold increased odds of albuminuria compared to those with LRG.Conclusion: The APOL1 risk variants are prevalent in children living in DRC. HRG carriers have increased odds of early kidney disease, and infection with HIV dramatically increases this probability.