Circulating miRNAs and their functional genetic variants in pseudoexfoliative glaucoma: potential of miR-146a-5p as a diagnostic biomarker

Purpose The etiology and pathogenesis of pseudoexfoliation syndrome (PEX) and its advancement into pseudoexfoliative glaucoma (PEG) are not fully understood. In this study, we aimed to evaluate the possible role played by two circulating microRNAs (miR-146a-5p and miR-196a-5p) in plasma and their functional genetic variants MIR146A rs2910164 and MIR196A2 rs11614913 in susceptibility to PEG or PEX. Methods Plasma miRNA relative expression of 27 patients with PEG, 25 patients with PEX and 27 controls was determined using quantitative RT-PCR, and fold change was calculated using the 2 −ΔΔCt method. Genotyping of 300 patients with PEG, 300 patients with PEX, and 300 controls was performed using a PCR-restriction fragment length polymorphism analysis. Result Plasma miR-146a-5p relative expression was significantly elevated in patients with PEG (3.9-fold) ( P < .000) and patients with PEX (2.7-fold) relative to controls ( P = .001). The diagnostic ability of plasma miR-146a-5p expression fold change was good for discriminating PEG vs. controls (AUC = 0.897, P < .000), and the optimal decision threshold was 1.83 (sensitivity = 74%, specificity = 93%). Plasma miR-196a-5p relative expression did not differ significantly between study groups. No significant difference in terms of the minor allele frequency or the distribution of genotypes for MIR146A rs2910164 G/C or MIR196A2 rs11614913 C/T was observed between study groups. Conclusions Circulating miR-146a-5p can contribute to the risk of PEX/PEG. Therefore, we propose that plasma miR-146a-5p can be developed as a potential biomarker for the minimally invasive diagnoses of PEX/PEG and as a potential therapeutic target with further studies.