Impact of variants in the VEGF gene on progression of proliferative diabetic retinopathy
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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.
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.
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).
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.
KeywordsVEFG Polymorphism Diabetic retinopathy
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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