Genetic polymorphisms and retinopathy of prematurity.

PURPOSE Retinopathy of prematurity (ROP) is a major problem among very preterm survivors of neonatal intensive care. Neovascularization of the retina is prominent in the proliferative stages of ROP and is under the control of several factors such as vascular endothelial growth factor (VEGF). This study was undertaken on the hypothesis that genetic polymorphisms of VEGF, transforming growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha would occur more frequently in preterm infants with progressive ROP than in those with mild or no disease. METHODS The frequencies of VEGF -634 G-->C, VEGF *936 C-->T, TNF-alpha -308 G-->A, and TGF-beta -509 C-->T were determined in DNA from 91 infants who had received treatment for threshold ROP and 97 comparison infants. RESULTS The frequencies of the VEGF *936 C-->T, TNF-alpha -308 G-->A and TGF-beta -509 C-->T polymorphisms were similar in both groups. The distribution of alleles at VEGF -634 was significantly different between the two groups (P = 0.03). Homozygotes for the G allele, associated with higher VEGF production were twice as likely to have threshold ROP. CONCLUSIONS The progression of ROP to threshold ROP in very preterm infants may be influenced by genetic differences in VEGF production. Future efforts at prevention of threshold ROP may be directed toward blocking excess production of VEGF.