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

Author

Listed:
  • Caroline Gluck

    (University of Pennsylvania
    University of Pennsylvania)

  • Chengxiang Qiu

    (University of Pennsylvania)

  • Sang Youb Han

    (Inje University College of Medicine)

  • Matthew Palmer

    (University of Pennsylvania)

  • Jihwan Park

    (University of Pennsylvania)

  • Yi-An Ko

    (University of Pennsylvania
    University of Pennsylvania)

  • Yuting Guan

    (University of Pennsylvania)

  • Xin Sheng

    (University of Pennsylvania)

  • Robert L. Hanson

    (Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases)

  • Jing Huang

    (University of Pennsylvania Perelman)

  • Yong Chen

    (University of Pennsylvania Perelman)

  • Ae Seo Deok Park

    (University of Pennsylvania)

  • Maria Concepcion Izquierdo

    (University of Pennsylvania)

  • Ioannis Mantzaris

    (Albert Einstein College of Medicine)

  • Amit Verma

    (Albert Einstein College of Medicine)

  • James Pullman

    (Department of Pathology Montefiore Medical Center)

  • Hongzhe Li

    (University of Pennsylvania Perelman)

  • Katalin Susztak

    (University of Pennsylvania
    University of Pennsylvania)

Abstract

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.

Suggested Citation

  • 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 Iz, 2019. "Kidney cytosine methylation changes improve renal function decline estimation in patients with diabetic kidney disease," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10378-8
    DOI: 10.1038/s41467-019-10378-8
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    Cited by:

    1. Laura J. Smyth & Emma H. Dahlström & Anna Syreeni & Katie Kerr & Jill Kilner & Ross Doyle & Eoin Brennan & Viji Nair & Damian Fermin & Robert G. Nelson & Helen C. Looker & Christopher Wooster & Darrel, 2022. "Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Poonam Dhillon & Kelly Ann Mulholland & Hailong Hu & Jihwan Park & Xin Sheng & Amin Abedini & Hongbo Liu & Allison Vassalotti & Junnan Wu & Katalin Susztak, 2023. "Increased levels of endogenous retroviruses trigger fibroinflammation and play a role in kidney disease development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Pascal Schlosser & Adrienne Tin & Pamela R. Matias-Garcia & Chris H. L. Thio & Roby Joehanes & Hongbo Liu & Antoine Weihs & Zhi Yu & Anselm Hoppmann & Franziska Grundner-Culemann & Josine L. Min & Ade, 2021. "Meta-analyses identify DNA methylation associated with kidney function and damage," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    4. Yu Yan & Hongbo Liu & Amin Abedini & Xin Sheng & Matthew Palmer & Hongzhe Li & Katalin Susztak, 2024. "Unraveling the epigenetic code: human kidney DNA methylation and chromatin dynamics in renal disease development," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Moh’d Mohanad Al-Dabet & Khurrum Shahzad & Ahmed Elwakiel & Alba Sulaj & Stefan Kopf & Fabian Bock & Ihsan Gadi & Silke Zimmermann & Rajiv Rana & Shruthi Krishnan & Dheerendra Gupta & Jayakumar Manoha, 2022. "Reversal of the renal hyperglycemic memory in diabetic kidney disease by targeting sustained tubular p21 expression," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Kelly Yichen Li & Claudia Ha Ting Tam & Hongbo Liu & Samantha Day & Cadmon King Poo Lim & Wing Yee So & Chuiguo Huang & Guozhi Jiang & Mai Shi & Heung Man Lee & Hui-yao Lan & Cheuk-Chun Szeto & Robert, 2023. "DNA methylation markers for kidney function and progression of diabetic kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Adrienne Tin & Pascal Schlosser & Pamela R. Matias-Garcia & Chris H. L. Thio & Roby Joehanes & Hongbo Liu & Zhi Yu & Antoine Weihs & Anselm Hoppmann & Franziska Grundner-Culemann & Josine L. Min & Vic, 2021. "Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus," Nature Communications, Nature, vol. 12(1), pages 1-18, December.

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