Abstract
This meta-analysis investigates the association between four gene polymorphisms - IL1A rs17561, IFN-γ rs2430561, STOX1 rs1341667, and PPAR-γ rs1801282 and the risk of preeclampsia (PE). Case-control studies published between 2005 and 2025 were retrieved from Scopus, PubMed, Web of Science and Google Scholar. The inclusion of newly available data enhances statistical power and offers an updated, reliable synthesis of evidence. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using MetaGenyo software across various genetic models. Power analysis validated statistical strength, and protein-protein interaction (PPI) networks were constructed using the database, STRING. A total of 14 research articles, including 3,151 PE cases and 6,101 controls data were analysed. The IL1A rs17561 polymorphism was significantly linked to preeclampsia (PE) susceptibility, demonstrating a protective effect under the recessive model (OR = 0.67) and an elevated risk for heterozygous carriers in the over-dominant model (OR = 1.49). Subgroup analyses were feasible for IFN-γ, STOX1, and PPAR-γ, but no significant associations were identified. Power analysis confirmed an adequate sample size, and PPI network analysis revealed interactions involving 8 nodes and 7 edges. The findings suggest that IL1A rs17561 has a variant-specific influence on preeclampsia risk, supporting the role of IL-1–mediated inflammation in its pathogenesis, while IFN-γ, STOX1, and PPAR-γ polymorphisms showed no significant associations.