Chronic heart failure and GPX3 promoter methylation: A clinical-epigenetic analysis

Selenoprotein GPX3 is linked to Chronic Heart Failure (CHF), but its promoter methylation patterns in CHF remain unclear.

To explore CpG methylation in the GPX3 promoter region and its association with clinical parameters in CHF.

Twenty CHF patients and twenty healthy controls were included. Methylation levels of CpG sites within the GPX3_FA28 promoter region were quantified. Group differences were assessed using appropriate statistical tests. Restricted cubic spline (RCS) models were applied to explore dose-response associations between differentially methylated CpG sites and clinical indicators across multiple physiological systems.

Significant locus-specific methylation alterations were identified in CHF patients. CpG_5 showed hypermethylation (P = 0.017), while CpG_9 (P = 0.045) and CpG_19 (P = 0.008) were hypomethylated compared with controls. Patients with NYHA class I/II exhibited higher methylation at CpG_1 (P = 0.028) and CpG_2 (P = 0.040). CpG_5 methylation displayed nonlinear associations (P < 0.05) with total bilirubin (inverted U-shape), carbon dioxide (triphasic), total cholesterol (U-shape), and plateletcrit (wave-like). CpG_9 correlated with activated partial thromboplastin time and hematopoietic markers, while CpG_19 was linked to eosinophil percentage and erythrocyte parameters.

GPX3 promoter methylation displays apparent locus specificity in CHF. Different CpG sites may contribute to CHF pathophysiology through distinct epigenetic mechanisms. These findings highlight the potential of GPX3 methylation as a stratified biomarker in CHF.