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

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Abstract

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.

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Acknowledgements

The authors thank the subjects for their participation in this study.

Funding

This study was supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK, 318S074). The sponsor or funding organization had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Department of Biomedical Engineering, TOBB University of Economics and Technology, 06560, Söğütözü, Ankara, Turkey

    Birsen Can Demirdöğen & Tuğba Öztürk Başer

  2. Department of Ophthalmology, Gülhane Training and Research Hospital, University of Health Sciences, Ankara, Turkey

    Mehmet Talay Köylü & Gökhan Özge

  3. Department of Ophthalmology, Ankara City Hospital, Ankara, Turkey

    Özlem Gürbüz Köz

  4. Department of Ophthalmology, Ankara Güven Hospital, Ankara, Turkey

    Tarkan Mumcuoğlu

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  1. Birsen Can Demirdöğen
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by TÖB, BCD, MTK and ÖGK. The first draft of the manuscript was written by BCD, and all authors commented on the manuscript. All authors read and approved the final manuscript.

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Correspondence to Birsen Can Demirdöğen.

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This study protocol was reviewed and approved by the Research Ethics Committee of University of Health Sciences (Date: 16.10.2018, decision no: 18/243). Written informed consent was obtained from participants.

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Can Demirdöğen, B., Öztürk Başer, T., Köylü, M.T. et al. Circulating miRNAs and their functional genetic variants in pseudoexfoliative glaucoma: potential of miR-146a-5p as a diagnostic biomarker. Int Ophthalmol 43, 3953–3967 (2023). https://doi.org/10.1007/s10792-023-02797-w

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