An association between vascular endothelial growth factor gene promoter polymorphisms and diabetic retinopathy.
BACKGROUND
Diabetic retinopathy is a highly prevalent cause of visual loss in Western countries. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor implicated in the development of the proliferative stage of this disease. Reports have suggested that polymorphisms at positions -460 and -634 of the 5' untranslated region of the VEGF gene increase its basal promoter activity.


METHODS
To investigate whether polymorphisms are associated with diabetic retinopathy, 215 patients with type 2 diabetes mellitus (T2DM) were enrolled. Among them, 82 subjects had proliferative diabetic retinopathy (PDR), 72 had non-proliferative diabetic retinopathy (NPDR), and 61 individuals without retinopathy served as controls. Two polymorphisms of the VEGF gene, a G-->C transversion at -634 (the G/C polymorphism) and a C-->T transition at -460 (the C/T polymorphism), were investigated by restriction fragment length polymorphism PCR and allele-specific PCR respectively.


RESULTS
We did not find any association between the C/T polymorphism and diabetic retinopathy. However, the G/C polymorphism genotype distribution and the frequency of the C allele were significantly higher in the NPDR group than in control patients (OR = 1.69, 95% CI = 1.03-2.79). Analysis of the distribution of combined genotypes of the VEGF gene revealed the prevalence of the C/C-C/C genotype in NPDR patients (OR = 8.26, 95% CI = 1.79-37.99) and C/G-CC in PDR patients (OR = 3.36, 95% CI = 1.39-8.12).


CONCLUSIONS
Occurrence of the -634C allele appears to be associated with increased VEGF gene promoter activity, and the G/C polymorphism might serve as a predictive factor for the development of diabetic retinopathy.
Szaflik
Jacek P
JP
Department of Ophthalmology, Medical University of Warsaw, Warsaw, Poland. jacek@amwaw.edu.pl
Wysocki
Tomasz
T
Kowalski
Michal
M
Majsterek
Ireneusz
I
Borucka
Anna I
AI
Blasiak
Janusz
J
Szaflik
Jerzy
J
D020121:5' Untranslated Regions / Q000235:genetics; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D020121:5' Untranslated Regions; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A