Genetic Associations of IL-2 (rs2069762) and EGR3 (rs3750192) Polymorphisms with Schizophrenia: A Meta-Analysis

Abstract Introduction: Schizophrenia (SCZ) is a severe mental illness influenced by genetic and environmental factors. Although genome-wide association studies (GWAS) have identified numerous genes linked to SCZ, their specific roles remain unclear. This meta-analysis explores the relationship between polymorphisms in the IL-2 (rs2069762) and EGR3 (rs3750192) genes and SCZ susceptibility. Methods: A systematic review of nine studies was conducted using databases such as PubMed, Google Scholar, and ScienceDirect. The studies examined the IL-2 and EGR3 polymorphisms and their associations with SCZ risk across different populations. Fixed and random-effect models were used to analyze allele, dominant, recessive, and overdominant models. Subgroup analyses were conducted by ethnicity. Results: For IL-2 (rs2069762), no significant associations with SCZ risk were found across all genetic models. The allele model (OR=0.94, p=0.34), dominant model (OR=0.85, p=0.55), recessive model (OR=0.93, p=0.76), and overdominant model (OR=0.94, p=0.76) all showed non-significant results. In contrast, EGR3 (rs3750192) demonstrated a significant association in the dominant model (OR=0.73, p=0.012) and the homozygous model (OR=0.70, p=0.004), suggesting a protective effect. Subgroup analysis revealed ethnic differences, with the Polish and Chinese groups showing significant protective effects for IL-2 and EGR3, respectively. Conclusion: While IL-2 (rs2069762) shows no consistent association with SCZ, EGR3 (rs3750192) may confer a protective effect, particularly in certain ethnic groups. Further research is required to confirm these findings and understand the genetic mechanisms underlying SCZ risk across populations.