Association of VEGF-1499C-->T polymorphism with diabetic nephropathy in type 1 diabetes mellitus

J Diabetes Complications. Jul-Aug 2007;21(4):242-5. doi: 10.1016/j.jdiacomp.2006.05.005.

Abstract

Vascular endothelial growth factor (VEGF) is reported to be implicated in the development of diabetic nephropathy. We performed a case-control study to determine if VEGF-2578C-->A, VEGF-1499C-->T, and VEGF-635G-->C single-nucleotide polymorphisms (SNPs) in the VEGF gene are associated with predisposition to diabetic nephropathy in type 1 diabetes. Genomic DNA was obtained from Irish type 1 diabetic individuals with nephropathy (cases, n=242) and those without nephropathy (controls, n=301), in addition to 400 healthy control samples. These samples were genotyped for the three SNPs using TaqMan or Pyrosequencing technology. Chi-squared analyses revealed no significant differences in genotype or allele frequencies in cases versus controls for VEGF-2578C-->A (genotype, P=.58; allele, P=.52) and VEGF-635G-->C (genotype, P=.58; allele, P=.33). However, a positive association with diabetic nephropathy was observed for the VEGF-1499T allele in the Northern Ireland population (P <.001) and subsequently replicated in a separate population from the Republic of Ireland (P <.001; combined, P <.001). Carriage of the VEGF-1499T allele was associated with a twofold excess risk of developing diabetic nephropathy (OR=2.24, 95% CI=1.50-3.36, P <.0001). No significant differences were found between the healthy control population and the type 1 diabetic population. Our results suggest that the VEGF-1499T allele, or an allele in linkage disequilibrium with this allele, is associated with susceptibility to diabetic nephropathy in the Irish population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Case-Control Studies
  • Cytidine / genetics*
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / etiology*
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / pathology
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide / genetics*
  • Thymidine / genetics
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Vascular Endothelial Growth Factor A
  • Cytidine
  • Thymidine