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A single genetic locus controls both expression of DPEP1/CHMP1A and kidney disease development via ferroptosis.
Guan, Yuting; Liang, Xiujie; Ma, Ziyuan; Hu, Hailong; Liu, Hongbo; Miao, Zhen; Linkermann, Andreas; Hellwege, Jacklyn N; Voight, Benjamin F; Susztak, Katalin.
Afiliação
  • Guan Y; Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Liang X; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Ma Z; Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Hu H; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Liu H; Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Miao Z; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Linkermann A; Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Hellwege JN; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Voight BF; Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Susztak K; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Nat Commun ; 12(1): 5078, 2021 08 23.
Article em En | MEDLINE | ID: mdl-34426578
Genome-wide association studies (GWAS) have identified loci for kidney disease, but the causal variants, genes, and pathways remain unknown. Here we identify two kidney disease genes Dipeptidase 1 (DPEP1) and Charged Multivesicular Body Protein 1 A (CHMP1A) via the triangulation of kidney function GWAS, human kidney expression, and methylation quantitative trait loci. Using single-cell chromatin accessibility and genome editing, we fine map the region that controls the expression of both genes. Mouse genetic models demonstrate the causal roles of both genes in kidney disease. Cellular studies indicate that both Dpep1 and Chmp1a are important regulators of a single pathway, ferroptosis and lead to kidney disease development via altering cellular iron trafficking.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Proteínas de Transporte Vesicular / Dipeptidases / Loci Gênicos / Ferroptose / Nefropatias Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Commun Ano de publicação: 2021 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Proteínas de Transporte Vesicular / Dipeptidases / Loci Gênicos / Ferroptose / Nefropatias Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Commun Ano de publicação: 2021 Tipo de documento: Article