Peripheral Expression Profiles of Glutathione Reductase and miR-144 in Patients with Atrial Fibrillation

Background: Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Glutathione reductase (GR) and microRNA-144 (miR-144) may participate in redox-related pathways. This study aimed to evaluate relative GSR mRNA and miR-144 expression in peripheral blood samples from patients with and without AF and to explore their associations with selected clinical characteristics. Methods: This case-control study included 189 hospitalized adults: 95 without AF and 94 with AF. Clinical, anthropometric, biochemical, and echocardiographic data were collected for all participants. GSR mRNA was assessed by quantitative real-time PCR in whole blood samples, whereas circulating miR-144 expression was evaluated in serum. Group differences were assessed using nonparametric tests, correlations were evaluated using Spearman's rank correlation coefficient, and multivariable logistic regression was used to identify variables independently associated with AF. Model stability was assessed using bootstrap internal validation. Results: Relative GSR mRNA expression was significantly lower in the AF group than in controls (0.1539 vs. 0.2058, p < 0.001), whereas miR-144 expression was significantly higher in patients with AF (0.3636 vs. 0.2550, p = 0.0183). In multivariable logistic regression adjusted for clinical confounders, higher miR-144 (OR = 1.336, p = 0.048) and lower GSR (OR = 0.343, p < 0.001) expression remained associated with AF. Bootstrap internal validation supported the statistical stability of the GSR association (optimism-corrected AUC = 0.709, bootstrapped 95% CI: 0.622-0.785), whereas miR-144 showed only a more modest and less stable association (optimism-corrected AUC = 0.598, bootstrapped 95% CI: 0.519-0.684); both signals remain exploratory and do not yet support routine clinical use as diagnostic or risk-stratification biomarkers in AF. Both markers showed exploratory correlations with selected clinical and biochemical variables. Given the cross-sectional design of the study, all reported relationships should be interpreted as statistical associations rather than as evidence of causality. The observed correlations between molecular markers and clinical parameters are hypothesis-generating and warrant further investigation.