May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Association of VEGF Gene Polymorphisms with Proliferative Diabetic Retinopathy in Type 2 Diabetics
Author Affiliations & Notes
  • V. S. Hau
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • Z. Tong
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • D. J. Cameron
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • D. Gibbs
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • L. P. Aiello
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • R. Avery
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • J. Harmon
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • E. Brinton
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • G. Brinton
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • K. Zhang
    Ophthalmology, University of Utah, Salt Lake City, Utah
  • Footnotes
    Commercial Relationships V.S. Hau, None; Z. Tong, None; D.J. Cameron, None; D. Gibbs, None; L.P. Aiello, None; R. Avery, None; J. Harmon, None; E. Brinton, None; G. Brinton, None; K. Zhang, None.
  • Footnotes
    Support NIH, Foundation Fighting Blindness, Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3242. doi:
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      V. S. Hau, Z. Tong, D. J. Cameron, D. Gibbs, L. P. Aiello, R. Avery, J. Harmon, E. Brinton, G. Brinton, K. Zhang; Association of VEGF Gene Polymorphisms with Proliferative Diabetic Retinopathy in Type 2 Diabetics. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3242.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: In the western world, type 2 diabetes is a growing epidemic known to cause serious microvascular complications such as proliferative diabetic retinopathy (PDR). It is thought that vascular endothelial growth factor (VEGF), a potent vascular permeability and angiogenic factor plays an important role in microvascular complications. Previous studies have linked specific VEGF polymorphisms with retinopathy, and have also shown ocular levels of VEGF are raised in the neovascular form of retinopathy.

Methods:: We conducted a case-control study where 116 cases (type 2 diabetics with PDR) and 46 controls (type 2 diabetics with 10+ years and no retinopathy) were genotyped for 2 single nucleotide polymorphisms (SNPs, rs1413711 and rs735286) in the promoter region of VEGF. Using DNA extracted from peripheral blood leukocytes, the specific regions of the VEGF polymorphisms were amplified by using site specific primers and subsequently purified. Next, a SNaPshot reaction was carried out according to protocol (Applied Biosystems, Foster, CA). Following thermocycling, the samples were analyzed using GeneScan Analysis on the ABI PRISM 3700. Results were confirmed by gene sequencing. Haplotype analysis was performed using Haploview software and analyzed by Pearson’s X2.

Results:: Individual analysis revealed that the C allele at rs1413711 was significantly associated with PDR. The C allele frequency was found to be 0.504 in cases (subjects with PDR) and 0.372 in controls (p=0.0358). No association was shown between rs735286 individually and PDR. However, rs1413711 and rs735286 are in fairly high linkage disequilibrium (R=0.87). Analysis of both SNPs revealed that CC was the risk haplotype for PDR. The frequency of CC was 0.210 in cases, and 0.108 in controls (p=0.0328), and the frequency of TT, the protective haplotype, was 0.011 in cases and 0.048 in controls (p=0.0359).

Conclusions:: These two SNPs may be important in influencing the transcription of VEGF leading to PDR and other microvascular complications of diabetes. Further understanding of which patients are at risk for PDR will help guide healthcare appropriations and target those who need more aggressive diabetic management.

Keywords: diabetic retinopathy • gene screening • retinal neovascularization 
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