Reduced Methylation of IRF5 Gene as a Biomarker for Gestational Diabetes Mellitus

BACKGROUND Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by insulin resistance. Emerging evidence suggests that epigenetic mechanisms, including DNA methylation, play a pivotal role in the pathophysiology of GDM. This study aimed to evaluate the methylation status of the interferon regulatory factors IRF5 and IRF7, which are key regulators of immune and inflammatory responses, in pregnant women with GDM. MATERIAL AND METHODS This study involved 62 pregnant women, including 39 with gestational diabetes mellitus and 23 healthy controls. The GDM diagnosis was based on the oral glucose tolerance test (OGTT), performed at 24 to 28 weeks of pregnancy. Peripheral blood samples were collected, and peripheral blood mononuclear cells (PBMCs) were isolated for DNA extraction. DNA methylation analysis was performed on the IRF5 and IRF7 gene promoters using quantitative methylation-specific PCR (Q-MSP). Statistical analysis was conducted using the Mann-Whitney U test for non-normally distributed data, and results were considered significant with a P value <0.05. RESULTS A significantly lower methylation level of the IRF5 gene was found in the GDM group compared to controls (median: 0.26 vs 0.42, P=0.027). No significant differences in IRF7 methylation were observed between the 2 groups (P=0.35). Methylation levels of IRF5 and IRF7 did not correlate with fasting plasma glucose (FPG), body mass index (BMI), or neonatal birth weight. CONCLUSIONS This study demonstrates that reduced IRF5 gene methylation is associated with GDM, suggesting a potential role of IRF5 hypomethylation in the inflammatory processes of the disease. The lack of methylation changes in IRF7 indicates its lesser relevance in GDM pathogenesis. These findings suggest that IRF5 methylation could serve as a novel epigenetic biomarker for GDM, independent of traditional clinical markers. Future studies should explore the functional role of IRF5 hypomethylation in GDM pathophysiology and its potential for early diagnosis and therapeutic intervention.