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

• Published in: Nature communications Vol. 10; no. 1; pp. 2461 - 12
• Main Authors: Gluck, Caroline, Qiu, Chengxiang, Han, Sang Youb, Palmer, Matthew, Park, Jihwan, Ko, Yi-An, Guan, Yuting, Sheng, Xin, Hanson, Robert L., Huang, Jing, Chen, Yong, Park, Ae Seo Deok, Izquierdo, Maria Concepcion, Mantzaris, Ioannis, Verma, Amit, Pullman, James, Li, Hongzhe, Susztak, Katalin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.06.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 45/22; 45/61; 45/77; 45/90; 631/208/176; 692/4022/1585/2759/1419; 692/699/1585/104; Aged; Case-Control Studies; CpG Islands; Cross-Sectional Studies; Cytosine; Cytosine - metabolism; Diabetes; Diabetes mellitus; Diabetic Nephropathies - genetics; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic nephropathy; Disease Progression; DNA Methylation; DNA probes; Epidermal growth factor; Epigenesis, Genetic; Female; Fibrosis; Gene expression; Gene Expression Regulation; Genomes; Glomerular Filtration Rate; Growth factors; Humanities and Social Sciences; Humans; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidneys; Male; Methylation; Middle Aged; multidisciplinary; Prediction models; Probes; Regulatory sequences; Renal function; Science; Science (multidisciplinary); Structural damage; Tubules
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-10378-8

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. Patients with diabetes commonly develop diabetic kidney disease (DKD). Here Gluck et al. identify a set of probes differentially methylated in renal samples from patients with DKD, and find that inclusion of these methylation probes improves current prediction models of renal function decline.