ANALYSIS OF GLOMERULAR TRANSCRIPTOMES FROM NEPHROTIC PATIENTS SUGGEST APOL1 RISK VARIANTS IMPACT PARIETAL EPITHELIAL CELLS DOI Open Access
Agustin Gonzalez‐Vicente, Dana C. Crawford, William S. Bush

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

The disproportionate risk for idiopathic proteinuric podocytopathies in Black people is explained, part, by the presence of two alleles (G1 or G2) APOL1 gene. pathogenic mechanisms responsible this genetic association remain incompletely understood. We analyzed glomerular RNASeq transcriptomes from patients with nephrotic syndrome which 72 had inferred African ancestry (AA) and 152 did not (noAA). Using gene coexpression networks we found a significant between allele number metamodule 2 (MM2), even after adjustment eGFR proteinuria at biopsy. Unadjusted Kaplan-Meier curves showed that unlike noAA, AA highest tertile MM2 activation scores were less likely to achieve complete remission (p≤0.014). Characteristic direction (ChDir) identified signature 1481 genes, separated those homozygous reference . Only AA, these genes was (p≤0.022) trend faster progression composite event kidney failure loss 40% (p≤0.099). ChDir significantly overlapped both enriched Epithelial Mesenchymal Transition inflammation terms. Finally, parietal epithelial cell (PEC)-identity but podocyte identity signature. Podocytes expressing variant APOL1s may generate inflammatory signals activate PECs paracrine contributing nephropathy.

Язык: Английский

ANALYSIS OF GLOMERULAR TRANSCRIPTOMES FROM NEPHROTIC PATIENTS SUGGEST APOL1 RISK VARIANTS IMPACT PARIETAL EPITHELIAL CELLS DOI Open Access
Agustin Gonzalez‐Vicente, Dana C. Crawford, William S. Bush

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

The disproportionate risk for idiopathic proteinuric podocytopathies in Black people is explained, part, by the presence of two alleles (G1 or G2) APOL1 gene. pathogenic mechanisms responsible this genetic association remain incompletely understood. We analyzed glomerular RNASeq transcriptomes from patients with nephrotic syndrome which 72 had inferred African ancestry (AA) and 152 did not (noAA). Using gene coexpression networks we found a significant between allele number metamodule 2 (MM2), even after adjustment eGFR proteinuria at biopsy. Unadjusted Kaplan-Meier curves showed that unlike noAA, AA highest tertile MM2 activation scores were less likely to achieve complete remission (p≤0.014). Characteristic direction (ChDir) identified signature 1481 genes, separated those homozygous reference . Only AA, these genes was (p≤0.022) trend faster progression composite event kidney failure loss 40% (p≤0.099). ChDir significantly overlapped both enriched Epithelial Mesenchymal Transition inflammation terms. Finally, parietal epithelial cell (PEC)-identity but podocyte identity signature. Podocytes expressing variant APOL1s may generate inflammatory signals activate PECs paracrine contributing nephropathy.

Язык: Английский

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