ArticleNature metabolism2023
Genetic susceptibility to diabetic kidney disease is linked to promoter variants of XOR.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 20 citations in OpenAlex.
- Canagliflozin Alleviates Diabetic Glomerular Endothelial Injury via Melibiose in a Microbiota-Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endothelial ferroptosis: a novel mechanism and therapeutic target in diabetic microvascular complications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Evaluation of Urine Exosome Lecithin Cholesterol Acyltransferase as a Biomarker for Diabetes Diagnosis and Dyslipidemia.Diabetes/metabolism research and reviews · 2026Article
- Gene modification: Exploring the potential in treating kidney diseases.Pharmacological research · 2026Review
- A New Quantitative Metric for Precise Classification of Diabetic Podocyte Injury Using Scanning Electron Microscopy.Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada · 2025Article
- Mild Hyperuricemia Attenuates Salt-Sensitive Hypertension and Kidney Damage.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Serum Metabolomics Reveals Potential Differences in Gut Microbiota-Associated Metabolites in Twins Discordant for Type 1 Diabetes.Diabetes · 2025Article
- Tubular Injury in Diabetic Kidney Disease: Early Diagnosis and Intervention Strategies.Diabetes/metabolism research and reviews · 2025Review
- The Contribution of Genetic Risk and Lifestyle Factors in the Progression of Diabetes to Diabetic Kidney Disease: A Prospective Cohort Study.Journal of diabetes · 2025Article
- Implication of xanthine oxidoreductase in oxidative stress-related chronic diseases.Frontiers in endocrinology · 2025Review
- The Renal Micro-Vasculopathy and Systemic Aldosterone-Renin Ratio (ARR) in Type 2 Diabetic Patients-A Retrospective Real-World Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- The association between vitamin D receptor gene polymorphism FokI and type 2 diabetic kidney disease and its molecular mechanism: a case control study.BMC medical genomics · 2024Article
- Aging kidneys reveal underlying mechanisms of endothelial dysfunction.Kidney international · 2024Article
- Emerging Roles of Xanthine Oxidoreductase in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- The presence of xanthine dehydrogenase is crucial for the maturation of the rat kidneys.Clinical science (London, England : 1979) · 2024Article
- Mitochondrial oxidative damage reprograms lipid metabolism of renal tubular epithelial cells in the diabetic kidney.Cellular and molecular life sciences : CMLS · 2024Article
- Redox regulation in diabetic kidney disease.American journal of physiology. Renal physiology · 2023Review
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21 authors at 6 institutions in 4 countries.
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Abstract
The lifetime risk of kidney disease in people with diabetes is 10-30%, implicating genetic predisposition in the cause of diabetic kidney disease (DKD). Here we identify an expression quantitative trait loci (QTLs) in the cis-acting regulatory region of the xanthine dehydrogenase, or xanthine oxidoreductase (Xor), a binding site for C/EBPβ, to be associated with diabetes-induced podocyte loss in DKD in male mice. We examine mouse inbred strains that are susceptible (DBA/2J) and resistant (C57BL/6J) to DKD, as well as a panel of recombinant inbred BXD mice, to map QTLs. We also uncover promoter XOR orthologue variants in humans associated with high risk of DKD. We introduced the risk variant into the 5'-regulatory region of XOR in DKD-resistant mice, which resulted in increased Xor activity associated with podocyte depletion, albuminuria, oxidative stress and damage restricted to the glomerular endothelium, which increase further with type 1 diabetes, high-fat diet and ageing. Therefore, differential regulation of Xor contributes to phenotypic consequences with diabetes and ageing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.