MicroRNA-related polymorphisms in pseudoexfoliation syndrome, pseudoexfoliative glaucoma, and primary open-angle glaucoma

ABSTRACT

Background: Pseudoexfoliation syndrome (PEX) and glaucoma (pseudoexfoliative glaucoma; PEXG, primary open-angle glaucoma; POAG) have mainly been studied for their associations with genes’ polymorphisms. The purpose of this exploratory study was to investigate the role of polymorphisms in genes encoding for micro RNAs (miRNAs) and in genes related to miRNA biogenesis.

Material and Methods: In the present genetic association study, ninety-two polymorphisms were investigated for their contribution to PEX (n = 203), PEXG (n = 38), and POAG (n = 40) pathogenesis compared to a control group (n = 188). The next generation sequencing (NGS) genotypic analysis revealed data for additional 28 variants.

Results: A protective association was found between PEX and polymorphism 11382316 (mir-3161) [odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47–0.86, p = 0.003], rs2155248 (mir-1304) [OR = 0.66, 95%CI: 0.47–0.94, p = 0.019], and rs28635903 (mir-1268a) [OR = 0.30, 95%CI: 0.10–0.94, p = 0.029]. Polymorphism rs113297757 (mir-3196) was associated with an increased risk of POAG [OR = 7.75, 95%CI: 2.13–28.76, p = 3 × 10⁻⁴]. Polymorphism rs1057035 (DICER) and rs55671916 (XPO5) in the 3ʹ-UTR of genes related to miRNA biogenesis was associated with decreased risk of PEX [OR = 0.65, 95%CI: 0.46–0.92, p = 0.014] and increased risk of PEXG [OR = 2.84, 95%CI: 1.02–7.94, p = 0.038], respectively. The aforementioned associations according to the allelic model were further supported by the genotypic models of statistical analyses.

Conclusions: This is the first study to report distinct associations of PEX, PEXG, and POAG in the same population with variants of genes involved in miRNA biogenesis and with miRNA genes’ polymorphisms. Further studies in larger groups of patients of various origins are needed to confirm the reported preliminary results.

KEYWORDS:

• Microrna
• polymorphism
• primary open-angle glaucoma
• Pseudoexfoliation syndrome
• pseudoexfoliative glaucoma

Declaration of interest

AC: No financial disclosures

PF: No financial disclosures

AM: No financial disclosures

FM: No financial disclosures

EB: No financial disclosures

EA: Honorarium from Allergan; travel grants from Allergan, Thea, and Novartis

TP: Honorarium from Allergan and Novartis

ABH: No financial disclosures

AL: No financial disclosures

FT: Grants/research support from Alcon, Pfizer, Novarrtis, Thea; Consultation fees from Alcon, Bayer, Allergan Pfizer, Thea; Company sponsored speakers bureau: Novartis, Thea, Alcon, Allergan, Santen

None of the authors has any financial interest or any conflict of interest related to the subject matter.

Additional information

Funding

This research is cofunded by the European Union (European Social Fund) and Greek national funds under the Act “Aristia” of the Operational Program “Education and Lifelong Learning” (Grant name “Aristia”—Grant number “1617”).