The Potential of ACE and MTHFR Polymorphism as Genetic Biomarker of Retinopathy of Prematurity : A Systematic Review and Meta-Analysis

Purpose: To investigate common polymorphisms in angiotensin converting enzyme (ACE) and methylene tetra hydro folate reductase (MTHFR) genes with retinopathy of prematurity (ROP) risk.Methods: A literature search was conducted in PubMed, Scopus, and Epistemonikos databases to retrievegenetic studies evaluating the relationship between ACE I/D, MTHFR-C677T, and ROP risk. Relevantstudies were selected and reviewed systematically according to the PRISMA guideline, and RevMan 5.4was used for data analysis.Results: There were 601 articles up to 2024 in the databases. Five articles were included formeta-analysis. Our analysis showed that ACE I/D was associated with ROP risk in II vs ID (odds ratio[OR]: 1.40, 95% confidence interval [CI] 1.12–1.74; I2: 76%) homozygous gene model II vs DD (OR:1.58, 95% CI 1.22–2.04; I2: 54%), and the allele model I vs. D (OR: 1.23, 95% CI 1.08–1.40; I2: 0%) were associated with higher chances to develop ROP. However, no associations of MTHFR polymorphism with ROP risk were found.Conclusions: ACE I/D polymorphism may serve as a genetic biomarker of increased ROP risk. TheMTHFR polymorphisms do not appear to influence susceptibility to ROP.Keywords: Angiotensin-converting enzyme, Meta-Analysis, Methylenetetrahydrofolate reductase,Polymorphism, Retinopathy of Prematurity