Abstract
Diabetes is a major cause of mortality and morbidity due to the long term microvascular complications of this disease. There is now convincing evidence to show that genetic factors together with elevated blood glucose play an important role in the susceptibility to diabetic nephropathy as well as retinopathy. The polyol pathway is thought to play an important role in the pathogenesis of diabetic microvascular complications. Aldose reductase is the first and rate-limiting enzyme of the polyol pathway. Polymorphisms in the promoter region as well as elsewhere in the gene have been associated with susceptibility to nephropathy, retinopathy as well as diabetic neuropathy. These associations have been replicated in patients with either type 1 or type 2 diabetes mellitus as well as across ethnic groups. These polymorphisms in the promoter region are also associated with expression of the gene. Although clinical trials using inhibitors of aldose reductase to treat diabetic microvascular complications have largely been unsuccessful, the identification of the susceptibility genes may help in the design of future drug regimens.
Keywords: diabetic nephropathy, retinopathy, neuropathy, diabetes, aldose reductase, polyol pathway, genetics
Current Medicinal Chemistry
Title: Polymorphisms of the Aldose Reductase Gene and Susceptibility to Diabetic Microvascular Complications
Volume: 10 Issue: 15
Author(s): A. G. Demaine
Affiliation:
Keywords: diabetic nephropathy, retinopathy, neuropathy, diabetes, aldose reductase, polyol pathway, genetics
Abstract: Diabetes is a major cause of mortality and morbidity due to the long term microvascular complications of this disease. There is now convincing evidence to show that genetic factors together with elevated blood glucose play an important role in the susceptibility to diabetic nephropathy as well as retinopathy. The polyol pathway is thought to play an important role in the pathogenesis of diabetic microvascular complications. Aldose reductase is the first and rate-limiting enzyme of the polyol pathway. Polymorphisms in the promoter region as well as elsewhere in the gene have been associated with susceptibility to nephropathy, retinopathy as well as diabetic neuropathy. These associations have been replicated in patients with either type 1 or type 2 diabetes mellitus as well as across ethnic groups. These polymorphisms in the promoter region are also associated with expression of the gene. Although clinical trials using inhibitors of aldose reductase to treat diabetic microvascular complications have largely been unsuccessful, the identification of the susceptibility genes may help in the design of future drug regimens.
Export Options
About this article
Cite this article as:
Demaine G. A., Polymorphisms of the Aldose Reductase Gene and Susceptibility to Diabetic Microvascular Complications, Current Medicinal Chemistry 2003; 10 (15) . https://dx.doi.org/10.2174/0929867033457359
DOI https://dx.doi.org/10.2174/0929867033457359 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Chronic Complications of Diabetes Mellitus: A Mini Review
Current Diabetes Reviews Advanced Glycation End Products: A Link Between Periodontitis and Diabetes Mellitus?
Current Diabetes Reviews Advent and Maturation of Regenerative Medicine
Current Stem Cell Research & Therapy Editorial
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Reactivity-Based Drug Discovery Using Vitamin B6-Derived Pharmacophores
Mini-Reviews in Medicinal Chemistry Pathogenetic Pathways of Cardiorenal Syndrome and their Possible Therapeutic Implications
Current Pharmaceutical Design Anti-Phospholipase A2 Receptor Autoantibody: A New Biomarker for Primary Membranous Nephropathy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) TAGE (Toxic AGEs) Theory in Diabetic Complications
Current Molecular Medicine Genetic Basis of Ureterocele
Current Genomics Drug Therapies in the Secondary Prevention of Cardiovascular Diseases:Successes, Shortcomings and Future Directions
Current Vascular Pharmacology Anthraquinones: Analytical Techniques as a Novel Tool to Investigate on the Triggering of Biological Targets
Current Drug Targets The Role of Lymphotoxin Receptor Signaling in Diseases
Current Molecular Medicine The Pleiotropic Effects of PPARs on Vascular Cells and Angiogenesis: Implications for Tissue Engineering
Current Stem Cell Research & Therapy Editorial: Do Some Glucagon-Like-Peptide-1 Receptor Agonists (GLP-1 RA) Reduce Macrovascular Complications of Type 2 Diabetes Mellitus? (A Commentary on the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) Trial)
Current Vascular Pharmacology Asymmetric Dimethylarginine (ADMA) and Cardiovascular Disease
Vascular Disease Prevention (Discontinued) Angiotensin II-Vasopressin Interactions in The Regulation of Cardiovascular Functions. Evidence for an Impaired Hormonal Sympathetic Reflex in Hypertension and Congestive Heart Failure
Endocrine, Metabolic & Immune Disorders - Drug Targets Puerarin: A Review on the Pharmacological Activity, Chemical Properties and Pharmacokinetics of Main Isoflavonoid
The Natural Products Journal Patients Stratification Strategies to Optimize the Effectiveness of Scavenging Biogenic Aldehydes: Towards a Neuroprotective Approach for Parkinson's Disease
Current Neuropharmacology Heme Oxygenase-1 in Tumor Biology and Therapy
Current Drug Targets Discovery of 6-Deoxydapagliflozin as a Highly Potent Sodium-dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes
Medicinal Chemistry