Polymorphism rs3742330 in microRNA Biogenesis Gene DICER1 Is Associated with Pseudoexfoliation Glaucoma in Saudi Cohort

Abstract

We investigated the association between DICER1 (rs3742330) and DROSHA (rs10719) polymorphisms and pseudoexfoliation glaucoma (PXG) and related clinical phenotypes in a Saudi cohort. In a retrospective case-control study, TaqMan real-time, PCR-based genotyping was performed in 340 participants with 246 controls and 94 PXG cases. The minor (G) allele frequency of rs3742330 in PXG (0.03) was significantly different from that in the controls (0.08) and protective against PXG (odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.16–0.92), p = 0.017). Similarly, the rs3742330 genotypes showed a significant protective association with PXG in dominant (p = 0.019, OR = 0.38, 95% CI = 0.15–0.92), over-dominant (p = 0.024, OR = 0.39, 95% CI = 0.16–0.95), and log-additive models (p = 0.017, OR = 0.38, 95% CI = 0.16–0.92). However, none remained significant after an adjustment for age, sex, and multiple testing. Rs10719 in DROSHA did not show any significant allelic or genotype association with PXG. However, a protective effect of the GA haplotype in DICER1 and DROSHA and PXG (p = 0.034) was observed. Both polymorphisms showed no significant effect on intraocular pressure and the cup–disk ratio. In conclusion, we report a significant genetic association between variant rs3742330 in DICER1, a gene involved in miRNA biogenesis, and PXG. Further investigation in a larger group of patients of different ethnicities and functional studies are warranted to replicate and validate its potential role in PXG.

The Importance of MicroRNA Expression in Pseudoexfoliation Syndrome

“…In recent years, an attempt has been made to investigate and describe the expression level of selected miRs in pseudoexfoliation syndrome. Four polymorphisms of genes isolated from the blood that may be related to PEX were identified and miR-122-5p was found to be upregulated in patient blood [ 26 , 29 , 31 ]. Furthermore, 18 miRs were identified with statistically different expressions in the aqueous humor [ 27 , 32 ].…”

“…Polymorphism rs3742330 in the gene DICER1 and rs10719 in DROSHA were investigated in patients’ blood using real-time PCR. A significant genetic association was reported between variant rs3742330 in DICER1 and PEXG [ 31 ].…”

“…Another report [ 31 ] investigated miR profiles of Korean patients with PEXG and normal-tension glaucoma compared to healthy individuals using aqueous humor samples. Ten downregulated miRs (miR-3156-5p, miR-4458, miR-6717-5p, miR-6728-5p, miR-6834-5p, miR-6864-5p, miR-6879-5p, miR-877-3p, miR-548e-3p, and miR-6777-5p) and two upregulated miRNAs (miR-30d-5p and miR-320a) in PEXG patients compared to the control were found.…”

“…Analyzing the existing literature, the following were used in research: a fragment of the anterior lens capsule, material from the aqueous humor, and blood, with divergent results [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

The 3’ UTR polymorphisms rs3742330 in DICER1 and rs10719 in DROSHA genes are not associated with primary open-angle and angle-closure glaucoma: As case-control study

“…Moreover, these polymorphisms have also been previously associated with several complex human diseases. These include hypertension, endometriosis, cancer, atherosclerosis, Parkinson’s, and pseudoexfoliation glaucoma [ 37 – 43 ].…”