ArticleThe Journal of clinical investigation2023
Reduced methylation correlates with diabetic nephropathy risk in type 1 diabetes.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Approach to Studies on Podocyte Lesions Mediated by Hyperglycemia: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Blood DNA methylation markers are associated with diabetic kidney disease progression in type 1 diabetes.Diabetologia · 2026Article
- Energy-sensing molecule RORγ regulates cholesterol metabolism and immune signaling in diabetic kidney disease and aging.Nature communications · 2026Article
- Regulatory networks of post-translational modifications in diabetic kidney disease: from pathogenic mechanisms to therapeutic frontiers.Frontiers in endocrinology · 2026Review
- New potential therapeutic targets of metabolic disorder-associated kidney disease and diabetic kidney disease.Kidney international · 2026Review
- Dedifferentiated proximal tubular epithelial cells in diabetic kidney disease: pathogenic roles, repair potential, and therapeutic implications.Frontiers in endocrinology · 2026Review
- From mechanisms to therapies: exploiting epigenetic and post-translational modifications of mitochondrial quality control in diabetic kidney disease.Frontiers in endocrinology · 2026Review
- Multi-Omics Integration IdentifiesInternational journal of molecular sciences · 2025Article
- Developmental programming: Differing impact of prenatal testosterone and prenatal bisphenol-A -treatment on hepatic methylome in female sheep.Molecular and cellular endocrinology · 2025Article
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- DNA Methylation Biomarkers Predict Offspring Metabolic Risk From Mothers With Hyperglycemia in Pregnancy.Diabetes · 2025Article
- GLUT1 and Cerebral Glucose Hypometabolism in Human Focal Cortical Dysplasia Is Associated with Hypermethylation of Key Glucose Regulatory Genes.Molecular neurobiology · 2025Article
- Clinical study of renal damage in patients with Type-1 diabetic nephropathy based on shear wave elastography and hemodynamics.Pakistan journal of medical sciences · 2025Article
- DNMT3B aggravated renal fibrosis in diabetic kidney disease via activating Wnt/β-catenin signaling pathway.Scientific reports · 2025Article
- The role of MBD2 in immune cell development, function, and autoimmune diseases.Cell death discovery · 2025Review
- CpG methylation changes associated with hyperglycemia in type 1 diabetes occur at angiogenic glomerular and retinal gene loci.Scientific reports · 2025Article
- Blood-Based Epigenetic Biomarkers Associated With Incident Chronic Kidney Disease in Individuals With Type 2 Diabetes.Diabetes · 2025Article
- Podocyte Death in Diabetic Kidney Disease: Potential Molecular Mechanisms and Therapeutic Targets.International journal of molecular sciences · 2024Review
- Integrated analysis of blood DNA methylation, genetic variants, circulating proteins, microRNAs, and kidney failure in type 1 diabetes.Science translational medicine · 2024Article
- Nucleic acid and protein methylation modification in renal diseases.Acta pharmacologica Sinica · 2024Review
Corrections and comments
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Authors and funding
32 authors at 11 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic nephropathy (DN) is a polygenic disorder with few risk variants showing robust replication in large-scale genome-wide association studies. To understand the role of DNA methylation, it is important to have the prevailing genomic view to distinguish key sequence elements that influence gene expression. This is particularly challenging for DN because genome-wide methylation patterns are poorly defined. While methylation is known to alter gene expression, the importance of this causal relationship is obscured by array-based technologies since coverage outside promoter regions is low. To overcome these challenges, we performed methylation sequencing using leukocytes derived from participants of the Finnish Diabetic Nephropathy (FinnDiane) type 1 diabetes (T1D) study (n = 39) that was subsequently replicated in a larger validation cohort (n = 296). Gene body-related regions made up more than 60% of the methylation differences and emphasized the importance of methylation sequencing. We observed differentially methylated genes associated with DN in 3 independent T1D registries originating from Denmark (n = 445), Hong Kong (n = 107), and Thailand (n = 130). Reduced DNA methylation at CTCF and Pol2B sites was tightly connected with DN pathways that include insulin signaling, lipid metabolism, and fibrosis. To define the pathophysiological significance of these population findings, methylation indices were assessed in human renal cells such as podocytes and proximal convoluted tubule cells. The expression of core genes was associated with reduced methylation, elevated CTCF and Pol2B binding, and the activation of insulin-signaling phosphoproteins in hyperglycemic cells. These experimental observations also closely parallel methylation-mediated regulation in human macrophages and vascular endothelial cells.
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