Comprehensive Systematic Review and Meta-Analysis of Solute Carrier Family 19, Member 1 (SLC19A1) G80A Gene Polymorphism and Its Association with Congenital Heart Defects in Fetal Development: Implications for Genetic Susceptibility and Prenatal Risk Assessment

Congenital heart defects (CHD) are a major cause of neonatal mortality, highlighting the importance of identifying genetic risk factors in fetal development. The SLC19A1 gene, encoding the reduced folate carrier, is critical for folate metabolism, essential for DNA synthesis during embryogenesis. The G80A polymorphism in SLC19A1 may influence folate transport efficiency and contribute to CHD risk. This meta-analysis aimed to investigate the association between SLC19A1 G80A polymorphism and CHD susceptibility. A systematic review of major databases, including PubMed and EMBASE, was conducted to identify relevant case-control studies. Genetic risk models, such as allele (A vs G), heterozygous (GA vs GG), homozygous (AA vs GG), dominant (GA + AA vs GG), and recessive (AA vs GG + GA), were analyzed using RevMan 5.4.1, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. Initial results across most genetic models did not show a significant association between G80A polymorphism and CHD. However, after excluding outliers, a moderate association was observed between the GA genotype and increased CHD risk (OR: 1.34, CI: 1.07-1.66). These findings suggest a minimal genetic effect, warranting further research in diverse populations.