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Impact of variants in the VEGF gene on progression of proliferative diabetic retinopathy

  • Retinal Disorders
  • Published:
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Abstract

Background

The development of diabetic retinopathy is associated with the duration of diabetes and HbA1c levels. However, the familial aggregation of diabetic retinopathy is consistent with genetic susceptibility. Recently, a –634C/G polymorphism in the vascular endothelial growth factor (VEGF) gene was shown to be associated with diabetic retinopathy. To clarify the contribution of the VEGF gene in the development of diabetic retinopathy we analyzed variants in this gene among 469 Japanese patients with type 2 diabetes.

Methods

DNA from each patient was typed for –634C/G and –2578C/A polymorphisms using conventional polymerase chain reaction techniques. The vitreous fluid samples were obtained from 40 patients with PDR for measurement of VEGF levels.

Results

We found a significantly higher frequency of the A allele in the group with proliferative diabetic retinopathy (PDR) than in the control group at –2578C/A polymorphism (p = 0.036). Moreover, if the subjects were grouped according to the duration of diabetes and status of diabetic retinopathy (a first group consisting of subjects with longer duration (>20 y) of diabetes without any retinopathy (n = 102), and a second group of those with shorter diabetes (<15 y) but having retinopathy (n = 35), the genotype distribution at -2578 C/A polymorphism was again significantly higher in the second group (p = 0.005) and differed significantly (p = 0.002) in a recessive model. The risk of the AA for PDR was 7.7 (95%, CI: 1.8–30.9).

Conclusions

The AA genotype at –2578C/A polymorphism in the VEGF gene is associated with proliferative diabetic retinopathy. No significant association with –634 C/G polymorphism was confirmed.

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific research on Priority Areas (C) Medical Genome Science from the Ministry of Education, Science, Culture and Sports of Japan to N.I.

We are indebted to the all participants of the study. We gratefully appreciate Dr. Takahiro Nakamura at The Institute of Physical and Chemical Research SNP Research Center of RIKEN for his statistical support. We also acknowledge technical assistance by Ms. Yumiko Sagisaka, Megumi Watanabe and Hisae Tomioka.

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Authors and Affiliations

  1. Department of Ophthalmology, Diabetes Center, Tokyo Women’s Medical University, 8–1, Kawada-cho, Shinjuku-ku, Tokyo, 162–8666, Japan

    Shinko Nakamura & Shigehiko Kitano

  2. Department of Medicine, Diabetes Center, Tokyo Women’s Medical University, Tokyo, Japan

    Naoko Iwasaki & Yasuhiko Iwamoto

  3. Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, Japan

    Naoko Iwasaki

  4. Institute of Medical Genetics, Tokyo Women’s Medical University, Tokyo, Japan

    Naoko Iwasaki

  5. Department of Ophthalmology, Tokyo Women’s Medical University Yachiyo Medical Center, Chiba, Japan

    Hideharu Funatsu

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  1. Shinko Nakamura
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  2. Naoko Iwasaki
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  3. Hideharu Funatsu
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Correspondence to Shinko Nakamura.

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There is no potential conflict of interest and no involvement of funding sources in this research.

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Nakamura, S., Iwasaki, N., Funatsu, H. et al. Impact of variants in the VEGF gene on progression of proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 247, 21–26 (2009). https://doi.org/10.1007/s00417-008-0915-3

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  • DOI: https://doi.org/10.1007/s00417-008-0915-3

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