Histopathologic findings associated with APOL1 risk variants in chronic kidney disease
Histopathologic findings associated with APOL1 risk variants in chronic kidney disease
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与慢性肾脏病 APOL1 风险变异相关的组织病理学发现
DOI：
10.1038/modpathol.2014.92
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发表时间：
2015-01-01
期刊：
影响因子：
7.5
通讯作者：
Freedman, Barry I.
中科院分区：
文献类型：
--
作者：
Larsen, Christopher P.;Beggs, Marjorie L.;Freedman, Barry I.
载脂蛋白L1基因（APOL 1）中肾病风险变异体对非裔美国人动脉肾硬化症或假定的高血压相关性肾病的肾组织病理学的影响尚不清楚。APOL 1基因型-表型相关性是在一个大型国家肾脏病理学实践中，以盲法从196名自报患有动脉肾硬化症的非裔美国人的肾活检中进行的。受试者患有慢性肾脏疾病，无肾病综合征。一项发现分析比较了58例有2个APOL 1风险变异的受试者与56例无APOL 1风险变异的受试者的肾小球和肾小管间质室的组织病理学变化。在另外82例风险变异为0、1和2的受试者的活检中进行了验证。通过卡方（2）分析评估两个风险变异与零风险变异组基因型和亚表型的相关性。ANOVA比较连续变量的平均值。在发现分析中，在有两个与零个APOL 1风险等位基因的患者中，观察到明显较少的陈旧性肾小球硬化，更多的（固化和消失）肾小球硬化，更多的甲状腺化型肾小管萎缩和更多的微囊肾小管扩张。具有零风险等位基因的人动脉硬化程度更高。节段性肾小球硬化在两组之间没有显著差异。发现时存在以下两种区别性组织病理学结果，即，
The effects of nephropathy risk variants in the apolipoprotein L1 gene (APOL1) on renal histopathology in African Americans with arterionephrosclerosis or putative 'hypertension-associated' nephropathy are unknown. APOL1 genotype-phenotype correlations were performed in a blinded manner from renal biopsies in 196 self-reported African Americans with arterionephrosclerosis on kidney biopsy at a large national nephropathology practice. Subjects had chronic kidney disease without nephrotic syndrome. A discovery analysis compared histopathologic changes in the glomerular and tubulointerstitial compartments in 58 subjects with 2 versus 56 subjects with 0 APOL1 risk variants. Validation was performed in biopsies from 82 additional subjects with 0, 1, and 2 risk variants. Two risk variant versus zero risk variant group genotype associations and subphenotypes were assessed by chi(2) analyses. ANOVA compared means of continuous variables. In discovery analyses, significantly less obsolescent glomerulosclerosis, more (solidified and disappearing) glomerulosclerosis, more thyroidization-type tubular atrophy, and more microcystic tubular dilatation were seen in patients with two versus zero APOL1 risk alleles. Greater degrees of arteriosclerosis were present in those with zero risk alleles. Segmental glomerulosclerosis did not differ significantly between groups. Presence of two of the following discriminatory histopathologic findings from discovery, that is,