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

Shinko Nakamura; Hideharu Funatsu; Shigehiko Kitano; Yasuhiko Iwamoto
January 2009
Graefe's Archive of Clinical & Experimental Ophthalmology;Jan2009, Vol. 247 Issue 1, p21
Academic Journal
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 (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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