An association between vascular endothelial growth factor gene promoter polymorphisms and diabetic retinopathy

Graefes Arch Clin Exp Ophthalmol. 2008 Jan;246(1):39-43. doi: 10.1007/s00417-007-0674-6. Epub 2007 Sep 12.

Abstract

Background: Diabetic retinopathy is a highly prevalent cause of visual loss in Western countries. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor implicated in the development of the proliferative stage of this disease. Reports have suggested that polymorphisms at positions -460 and -634 of the 5' untranslated region of the VEGF gene increase its basal promoter activity.

Methods: To investigate whether polymorphisms are associated with diabetic retinopathy, 215 patients with type 2 diabetes mellitus (T2DM) were enrolled. Among them, 82 subjects had proliferative diabetic retinopathy (PDR), 72 had non-proliferative diabetic retinopathy (NPDR), and 61 individuals without retinopathy served as controls. Two polymorphisms of the VEGF gene, a G-->C transversion at -634 (the G/C polymorphism) and a C-->T transition at -460 (the C/T polymorphism), were investigated by restriction fragment length polymorphism PCR and allele-specific PCR respectively.

Results: We did not find any association between the C/T polymorphism and diabetic retinopathy. However, the G/C polymorphism genotype distribution and the frequency of the C allele were significantly higher in the NPDR group than in control patients (OR = 1.69, 95% CI = 1.03-2.79). Analysis of the distribution of combined genotypes of the VEGF gene revealed the prevalence of the C/C-C/C genotype in NPDR patients (OR = 8.26, 95% CI = 1.79-37.99) and C/G-CC in PDR patients (OR = 3.36, 95% CI = 1.39-8.12).

Conclusions: Occurrence of the -634C allele appears to be associated with increased VEGF gene promoter activity, and the G/C polymorphism might serve as a predictive factor for the development of diabetic retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Aged
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetic Retinopathy / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • 5' Untranslated Regions
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A