Functional VEGF C-634G Polymorphism Is Associated With Development of Diabetic Macular Edema and Correlated With Macular Retinal Thickness in Type 2 Diabetes

Biochem Biophys Res Commun. 2005 Aug 5;333(3):679-85. doi: 10.1016/j.bbrc.2005.05.167.


Since vascular endothelial growth factor (VEGF) has a strong effect on induction of vascular permeability, VEGF is an attractive candidate gene for development of diabetic macular edema (ME). Among the 378 patients with type 2 diabetes studied, 203 patients had no retinopathy, 93 had non-proliferative diabetic retinopathy (NPDR), and 82 had proliferative diabetic retinopathy (PDR). ME was present in 16 patients with NPDR and 47 patients with PDR. We genotyped three VEGF polymorphisms: C-2,578A, G-1,154A, and C-634G. Genotype and allele distribution of C-634G, but not C-2,578A or G-1,154A, were significantly different between patients with and without diabetic retinopathy. Logistic regression analysis revealed that the C-634G genotype was a risk factor for DR (p = 0.002), and furthermore for ME (p = 0.047), independently from severity of DR, with the -634C allele increasing the risk. Macular thickness measured by optical coherence tomography was correlated with the C-634G genotype, with the trend increasing with the presence of more -634C alleles (p = 0.006). Stepwise regression analysis showed that duration of diabetes and presence of the C-634G genotype were independent predictors of macular thickness. In addition, basic transcriptional activity levels associated with the -634C allele were greater compared to those seen with the -634G allele in human glioma and lymphoblastic T-lymphocyte cells. These results demonstrate that the VEGF C-634G polymorphism is a genetic risk factor for ME as well as DR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • DNA Primers
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetic Retinopathy / genetics
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Macular Edema / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Vascular Endothelial Growth Factor A / genetics*


  • DNA Primers
  • Vascular Endothelial Growth Factor A