MOLECULAR HETEROGENEITY OF PRE-ECLAMPSIA: COMPARATIVE PROFILING OF INFLAMMATORY, ANGIOGENIC, AND METABOLIC GENE EXPRESSION IN EARLY VERSUS LATE ONSET
DOI:
https://doi.org/10.22159/ajpcr.2026v19i6.59478Keywords:
Pre-eclampsia, Early-onset, Late-onset, Tumor necrosis factor-α, Interleukin-10, Vascular endothelial growth factor, Lipoprotein lipase,, Gene expression.Abstract
Objectives: Pre-eclampsia is a heterogeneous pregnancy-specific disorder. This study aimed to investigate the differential gene expression of inflammatory (tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]), angiogenic vascular endothelial growth factor (VEGF), and metabolic lipoprotein lipase (LPL) markers in early-onset pre-eclampsia (EOPE), late-onset pre-eclampsia (LOPE), and healthy pregnant controls.
Methods: A hospital-based case–control study was conducted with 200 pregnant women (50 EOPE, 50 LOPE, and 100 normotensive controls). Gene expression was analyzed in peripheral blood mononuclear cells using quantitative real-time polymerase chain reaction. Relative expression was calculated by the 2^–ΔCt method using glyceraldehyde-3-phosphate dehydrogenase as the reference gene. Statistical analysis was performed using one-way analysis of variance with post hoc tests.
Results: Both EOPE and LOPE showed significant upregulation of TNF-α (EOPE: 3.86±0.55; LOPE: 3.78±0.46 vs. Control: 5.34±1.86; p<0.001) and downregulation of IL-10 (EOPE: 7.46±0.57; LOPE: 7.21±0.78 vs. Control: 6.20±0.95; p<0.001), with more pronounced IL-10 suppression in EOPE. VEGF expression was significantly upregulated in both subtypes (EOPE: 5.20±0.50; LOPE: 5.11±0.53 vs. Control: 5.61±0.76; p<0.001). LPL expression was significantly higher in LOPE (2.84±0.39) compared to EOPE (3.02±0.27) and controls (3.09±0.37; p=0.0003). EOPE was associated with earlier onset, higher blood pressure, and greater proteinuria (p<0.001).
Conclusion: The study demonstrates distinct molecular profiles between EOPE and LOPE, characterized by intense inflammatory dysregulation in EOPE and relatively enhanced angiogenic and metabolic gene expression in LOPE. These findings support the concept of molecular heterogeneity in pre-eclampsia and highlight TNF-α, IL-10, VEGF, and LPL as potential biomarkers for subtype-specific risk stratification and targeted management.
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