Susceptibility genes for diabetic nephropathy in type 1 diabetes : Studies of five genes involved in glucose metabolism, glomerular structure, and blood pressure regulation
Year: 2004
Type: dissertation
Study design: Observational Study
Abstract: Introduction: A third of all patients with type 1 diabetes develop diabetic nephropathy within 10 to 30 years, which leads to a decline in renal function and eventually to dialysis or renal transplantation.This complication is associated with a 40-fold increase in the incidence of cardiovascular disease and premature death.Substantial evidence exists for genetic factors in the development and progression of the disease.The present study was undertaken to investigate gene variations that may play a role in the pathogenesis of diabetic nephropathy and its related traits. Subjects and methods:The study uses a cross-sectional, case-control design comprising 996 patients with type 1 diabetes.All patients were recruited from 20 referral centers as a part of a nationwide multi-center study, the FinnDiane study.They were classified into four groups according to their urinary albumin excretion rate.A number of previously characterized polymorphisms in the genes investigated were selected for each study.The polymorphic region was amplified by polymerase chain reaction, and genotyping was performed by a solid-phase minisequencing method.Results: The AA genotype of the functional -374 T/A polymorphism in the RAGE gene located on chromosome 6p21.3had a protective effect against proteinuria in patients with poor glycemic control, and against macrovascular disease.The Pro7 allele of the Leu7Pro polymorphism of preproneuropeptide Y on chromosome 7p15.1 was associated with poor glycemic control, proteinuria, higher triglycerides, and coronary heart disease.The AA haplotype of the X-chromosomal AT2 gene was associated with a decline in renal function and an increase in pulse pressure in males.Polymorphisms of the nephrin and the DRD3 gene on chromosome 3q13.3associated neither with diabetic nephropathy, amount of proteinuria, serum lipids nor blood pressure.Conclusion: This study suggests a gene-environment effect between the RAGE gene and diabetic nephropathy.The AT2 gene may play a role in the male predominance of diabetic nephropathy by influencing renal function and premature aging of the vascular tree.The Pro7 allele of preproneuropeptide Y may be involved in the pathogenesis of diabetic nephropathy through an impairment of glycemic control and lipids.No evidence appeared for any involvement of the DRD3 or the nephrin gene in diabetic late complications.patients with type 2 diabetes.
Source: Työväentutkimus Vuosikirja
Author: Kim Pettersson-Fernholm
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1173106924