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

Abstract

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.

KEYWORDS::

• Genetic polymorphisms
• HGF/c-Met
• ROP
• VEGF/VEGF-receptor

ACKNOWLEDGMENT

The authors are grateful to Belgin Ünal, PhD, Department of Public Health, Dokuz Eylul University, Izmir, Turkey, for statistical analysis.

Declaration of interest: This work was supported by Dokuz Eylul University Research Foundation via project number 07.KB.SAG.048. The authors report no conflicts of interest.