The clinical role of vascular endothelial growth factor (VEGF) system in the pathogenesis of retinopathy of prematurity.
BACKGROUND
Recent experimental studies suggest that vascular endothelial growth factor (VEGF) can play an important role in the development of retinopathy of prematurity (ROP). There are interesting observations of VEGF concentration in the serum, depending on its gene polymorphism which can have an impact on abnormal vessel development in the retina.


OBJECTIVE
Analysis of: (1) association of VEGF gene polymorphisms and the incidence of ROP, (2) correlation between serum concentration of VEGF and soluble VEGF receptor 1 (sVEGFR-1) during the 1st month of life and the risk of ROP, and (3) correlation between VEGF gene polymorphisms and VEGF serum concentrations.


METHODS
A sample of 181 newborns with mean birthweight 1054 g (range: 500-1500 g) was prospectively evaluated. Molecular analysis of VEGF -460T>C and 405G>C polymorphisms were performed in the whole studied population, and concentrations of VEGF and sVEGFR-1 were measured by Elisa assay in the 2nd, 3rd and 4th weeks of life in the group of 128 children. The infants were divided into 3 groups: A) no ROP (n = 101), B) ROP not requiring treatment (n = 20), and C) ROP requiring laser or cryotherapy (n = 60).


RESULTS
The frequency of VEGF 405G>C polymorphism was similar in all studied groups. The carriage of polymorphic allele -460 T was significantly overrepresented in ROP newborns who required treatment as compared to the no ROP group (54.2% vs 42.6%; OR: 1.63; 95% CI: 1.03-2.55). VEGF serum concentrations in the patients ascribed to different groups depending on the 405G>C or -460 T>C polymorphisms were similar. VEGF and sVEGFR-1 concentration on the 10th day of life did not differ significantly between the studied groups. Consecutive measurements showed a gradual increase in VEGF serum concentration in children without ROP, whereas in children with ROP requiring treatment the levels remained low.


CONCLUSIONS
Based on our observations and previously published data, the association of the VEGF gene promoter polymorphisms and the risk of advanced ROP is weak. VEGF serum concentration assessment as early as on the 20th day of life appears to be a promising approach to recognize newborns at risk of the development of advanced ROP.
Department of Pediatrics, Jagiellonian University, 30-663, Cracow, Poland, kwintap@mp.pl.
Przemko
P
Kwinta
Mirosław
M
Bik-Multanowski
Zofia
Z
Mitkowska
Tomasz
T
Tomasik
Jacek J
JJ
Pietrzyk
D001724:Birth Weight; D003452:Cryosurgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D017075:Laser Coagulation; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012178:Retinopathy of Prematurity / Q000097:blood / Q000235:genetics* / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1