Research Article: Association of Apolipoprotein E Gene Polymorphism with Type Diabetic Nephropathy in the Southern Chinese Population
Abstract:
Diabetic nephropathy (DN) is one of the major complication of type diabetes mellitus (TDM) and the leading cause of end-stage renal disease (ESRD) or chronic kidney disease (CKD).– It is estimated that around % of individuals with diabetes will develop DN. By , the projected incidence of ESRD in the United States is estimated to be between , and ,, cases. In Europe, approximately % of new diabetic patients requiring dialysis treatment are due to DN. In China, the prevalence and incidence of DN have also increased dramatically over the past decade, affecting approximately . million individuals. DN is characterized by the presence of mass proteinuria, hypertension, renal failure, and persistent albuminuria (> mg/ hours). Risk factors for DN include race, systemic hypertension, age, hyperglycemia, male gender, smoking, dyslipidemia and genetic factors.– DN not only leads to kidney impairment but has also been associated with an increased risk of atrial fibrillation (AF), colorectum cancer, liver cancer, larynx cancer and mitochondrial dysfunction.– Diabetic dyslipidemia is characterized by elevated levels of triglycerides, LDL-cholesterol, low levels of HDL-cholesterol, and an abundance of small dense LDL particles.– Although the pathogenesis of DN is complex and not yet fully understood, previous studies have identified a correlation between DN and various proteins involved in lipid metabolism.– Dyslipidemia contributes to the deposition of lipids in the kidney, leading to inflammation, lipotoxicity, podocyte dysfunction, and fibrosis, ultimately resulting in the development of DN. These lipid alterations or abnormalities in lipoproteins increase the risk of nephropathy in individuals with diabetes., Apolipoproteins play a crucial role in lipid metabolism by interacting with plasma lipids to form lipoproteins, which are soluble lipid-protein complexes. Apolipoprotein E (APOE) is a polymorphic glycoprotein that plays a key role in dyslipidemia., APOE accomplishes its lipid metabolism mainly through binding to LDL receptors and mediating the removal of chylomicron remnants and VLDL from serum. Both VLDL and chylomicron particles become enriched in APOE as they circulate through the capillaries and are lipolyzed on the surface of endothelial cells by lipoprotein lipase. This enzyme hydrolyzes triglycerides, releasing fatty acids that serve as energy sources for cell utilization. In this manner, APOE plays a crucial role in directing the metabolism of both endogenous triglycerides and VLDL and dietary triglycerides and chylomicrons. It accomplishes this by delivering these lipids either to extrahepatic cells (via VLDL and their remnants) or to the liver (via chylomicron remnants). In the liver, dietary fatty acids can be metabolized or resecreted as triglycerides with VLDL, while cholesterol is eliminated through the bile. In this context, APOE exhibits an “endocrine-like” functionality. Additionally, it can redistribute lipids among various cells within a tissue, thereby fulfilling a “paracrine-like” role in lipid transport and delivery.
Introduction:
Diabetic nephropathy (DN) is one of the major complication of type diabetes mellitus (TDM) and the leading cause of end-stage renal disease (ESRD) or chronic kidney disease (CKD). – It is estimated that around % of individuals with diabetes will develop DN. By , the projected incidence of ESRD in the United States is estimated to be between , and ,, cases. In Europe, approximately % of new diabetic patients requiring dialysis treatment are due to DN. In China, the prevalence and incidence of DN have also increased…
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