Influence of polymorphisms in VEGF, TNF-alpha, and GSTP1 genes on retinopathy of prematurity risk: a Meta-analysis

Purpose: To investigate the influence of polymorphisms in vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), and glutathione S-transferase Pi isoform (GSTP1) genes on retinopathy of prematurity (ROP) risk, we performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant meta-analysis. Methods: An exhaustive search was conducted in PubMed, Web of Science, and CNKI for genetic studies evaluating the relationship between VEGF (-460 T/C, +936 C/T, -634 G/C, and -2578 C/A), TNF-alpha (-308 G/A) and GSTP1 (Ile/Val) polymorphisms and ROP risk from inception until November 2019. Odds ratio (OR) with the 95% confidence interval (CI) were used for estimating combined effect size. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Results: A total of 14 studies met the inclusion criteria. The meta-analyses revealed that VEGF - 460 T/C was associated with ROP risk in the allele model (C vs. T, OR = 0.83, 95% CI: 0.74-0.94, P-OR=0.004), homozygous gene model (CC vs. TT, OR = 0.70, 95% CI: 0.54-0.91, P-OR=0.008), dominant gene model (CC + TC vs. TT, OR = 0.80, 95% CI: 0.67-0.95, P-OR = 0.012), and recessive gene model (CC vs. TC + TT, OR = 0.74, 95% CI: 0.59-0.94, P-OR = 0.014). However, we did not find significant differences in the genotype and allele distribution of VEGF + 936 C/T, -634 G/C, -2578 C/A, TNF-alpha - 308 G/A and GSTP1 Ile/Val polymorphisms, between ROP and control group (p > .05). Conclusions: VEGF polymorphism -460 T/C was associated with a lower ROP risk. Further research is warranted to investigate haplotype effects of VEGF polymorphisms on the risk of ROP.