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Kidney cytosine methylation changes improve renal function decline estimation in patients with diabetic kidney disease.

Caroline Gluck | Chengxiang Qiu | Sang Youb Han | Matthew Palmer | Jihwan Park | Yi-An Ko | Yuting Guan | Xin Sheng | Robert L Hanson | Jing Huang | Yong Chen | Ae Seo Deok Park | Maria Concepcion Izquierdo | Ioannis Mantzaris | Amit Verma | James Pullman | Hongzhe Li | Katalin Susztak
Nature communications | 2019

Epigenetic changes might provide the biological explanation for the long-lasting impact of metabolic alterations of diabetic kidney disease development. Here we examined cytosine methylation of human kidney tubules using Illumina Infinium 450 K arrays from 91 subjects with and without diabetes and varying degrees of kidney disease using a cross-sectional design. We identify cytosine methylation changes associated with kidney structural damage and build a model for kidney function decline. We find that the methylation levels of 65 probes are associated with the degree of kidney fibrosis at genome wide significance. In total 471 probes improve the model for kidney function decline. Methylation probes associated with kidney damage and functional decline enrich on kidney regulatory regions and associate with gene expression changes, including epidermal growth factor (EGF). Altogether, our work shows that kidney methylation differences can be detected in patients with diabetic kidney disease and improve kidney function decline models indicating that they are potentially functionally important.

Pubmed ID: 31165727

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: F32 DK112635
  • Agency: NIDDK NIH HHS, United States
    Id: DP3 DK108220
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK087635
  • Agency: U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases), International
    Id: RO1 DK087635
  • Agency: U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases), International
    Id: F32 DK112635
  • Agency: U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases), International
    Id: DP3 DK108220

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This is a list of tools and resources that we have found mentioned in this publication.


UCSC Genome Browser (tool)

RRID:SCR_005780

Portal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.

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RnBeads (tool)

RRID:SCR_010958

An R package for comprehensive analysis of DNA methylation data obtained with any experimental protocol that provides single-CpG resolution, including Infinium 450K microarray and bisulfite sequencing protocols, but also MeDIP-seq and MBD-seq.

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