Associations of VEGF/VEGF-Receptor and HGF/c-Met Promoter Polymorphisms With Progression/Regression of Retinopathy of Prematurity

Purpose: To determine the effect(s) of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), hepatocyte growth factor (HGF), and HGF receptor (c-Met) polymorphisms on progression/regression of retinopathy of prematurity (ROP) in premature infants. Materials and methods: This study comprised both a prospective analysis and a clinically relevant laboratory investigation. Enrolled were 123 Turkish preterm infants-gestational age (GA), <= 34 weeks; birth weight (BW), <= 1500 g-from a single tertiary care center. Infants were grouped as those who had undergone laser therapy (Group 1, n = 42), those with spontaneously regressed ROP (Group 2, n = 50), and those with no ROP (controls) (Group 3, n = 31). VEGF(-634) C and VEGF(-460) C polymorphisms were analyzed using the PCR-restriction fragment length polymorphism (RFLP) (PCR-RFLP) technique. VEGFR-2, HGF, and c-Met gene promoter polymorphisms were determined by direct sequencing. Results: Mean GAs and BWs of infants in Groups 1 and 2 were statistically significantly lower than those of Group 3 (p = 0.001). Frequencies of VEGF(-634) C and VEGF(-460) C polymorphisms were similar for all groups. We found a +32G -> A single-nucleotide polymorphism (SNP) in the promoter region of the VEGFR-2 gene. HGF and c-Met gene promoter polymorphisms were not found in any group. Conclusions: Our results indicate that there is no association between the carrier states of gene promoter polymorphisms VEGF(-634) C, VEGF(-460) C, and VEGFR-2, and progression or spontaneous regression of ROP in preterm infants. The absence of HGF and c-Met polymorphisms in our study groups suggests that polymorphisms in the minimal promoters of these genes are not involved in the pathogenesis of ROP.