Genetic Variants and Risk Factors in Diabetic Nephropathy
Summary
Diabetic nephropathy arises from complex interactions between prolonged hyperglycaemia, haemodynamic stress and individual genetic susceptibility. Central to its pathogenesis are glomerular basement membrane thickening, mesangial matrix expansion and podocyte loss, which collectively impair filtration. Genetic studies have identified polymorphisms in genes regulating the renin–angiotensin system, inflammatory mediators, lipid metabolism and growth factors. For example, insertion/deletion variants in the ACE gene influence intraglomerular pressure, while single nucleotide polymorphisms in TCF7L2, VEGF and MCP-1 modulate inflammatory and angiogenic pathways. Variants in apolipoprotein E and peroxisome proliferator-activated receptor gamma affect lipid homeostasis and oxidative stress responses, further contributing to glomerular injury. Epigenetic modifications and gene–environment interactions amplify risk, as poor glycaemic control and hypertension potentiate genetically mediated pathways. Identifying high-risk genotypes offers a route to stratified surveillance, early intervention and tailored therapeutics, with the potential to delay progression to end-stage renal disease.
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Genetic Variants and Risk Factors in Diabetic Nephropathy publication trend
The graph below shows the total number of articles in genetic variants and risk factors in diabetic nephropathy across all publications each year (not limited to Nature Index journals).
Technical terms
Single nucleotide polymorphism (SNP): A variation at a single base position in the DNA sequence that may affect gene function or regulation.
Genome-wide association study (GWAS): An approach that scans the entire genome to identify genetic variants associated with a particular disease.
Mesangial expansion: An increase in the supportive matrix and cell content of the glomerular mesangium, contributing to impaired filtration.
Albumin-to-creatinine ratio (ACR): A clinical measure of albumin excretion used to detect and monitor kidney damage.
Estimated glomerular filtration rate (eGFR): A calculation based on serum creatinine that estimates the rate of blood filtration by the kidneys.
References
- IGF1 and PPARG polymorphisms are associated with reduced estimated glomerular filtration rate in a cohort of children and adolescents with type 1 diabetes. Acta Diabetologica (2023).
- Effects of APOE isoforms in diabetic nephropathy patients of South India. Acta Diabetologica (2024).
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