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 and Katalin Susztak ()
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Caroline Gluck: 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
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

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10378-8

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