Association of vascular endothelial growth factor, transforming growth factor beta, and interferon gamma gene polymorphisms with proliferative diabetic retinopathy in patients with type 2 diabetes

Mol Vis. 2012:18:2749-57. Epub 2012 Nov 17.


Purpose: Chronic hyperglycemia and hypoxemia are believed to be causal factors in the development of proliferative diabetic retinopathy (PDR) among individuals with type 2 diabetes. It is hypothesized that formation of new blood vessels in the retina due to prolonged hypoxia is associated with increased expression of several growth factors and angiogenic cytokines. In the present study, we investigated the association of genetic polymorphisms in vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and interferon γ (IFN-γ) genes, which may be responsible for the hypoxia-induced VEGF-mediated neovascularization pathway for the pathogenesis of PDR.

Methods: Our case-control association study composed of 493 ethnically matched volunteers (253 with PDR [cases] and 240 diabetic controls [DC]). Gene polymorphisms were determined with Taqman-based real-time PCR and amplification refractory mutation analysis system PCR.

Results: The VEGF-460C (rs833061C; p=0.0043) and IFN-γ +874T (rs2430561T; p=0.0011) alleles were significantly associated with PDR.

Conclusions: Genetic variations at VEGF-460C and IFN-γ +874T might accelerate the pathogenesis of retinal neovascularization in PDR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Retinopathy / complications
  • Diabetic Retinopathy / genetics*
  • Diabetic Retinopathy / pathology
  • Female
  • Gene Frequency
  • Humans
  • Interferon-gamma / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Real-Time Polymerase Chain Reaction
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Neovascularization / complications
  • Retinal Neovascularization / genetics*
  • Retinal Neovascularization / pathology
  • Sequence Analysis, DNA
  • Transforming Growth Factor beta / genetics*
  • Vascular Endothelial Growth Factor A / genetics*


  • Transforming Growth Factor beta
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Interferon-gamma