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

Altaf A Kondkar,Tahira Sultan,Glenn P Lobo,Faisal A Almobarak,Taif A Azad,Rakesh Radhakrishnan,Saleh A Al-Obeidan,Essam A Osman

doi:10.3390/genes13030489

Altaf A Kondkar, Tahira Sultan + Show 6 more

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https://doi.org/10.3390/genes13030489

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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.

Highlights

Pseudoexfoliation glaucoma (PXG) is an age-related and more aggressive form of open-angle glaucoma associated with a poor prognosis
PXG is characterized by excessive production and abnormal accumulation or deposition of pseudoexfoliative material, typically in the anterior segment of the eye that obstructs the aqueous flow pathway, leading to increased intraocular pressure (IOP), optic nerve head damage, retinal ganglion cell death (RGC), and subsequent loss of vision [1,2]
We report for the first time a moderate allelic association of variant rs3742330 (G) in DICER1 with PXG in a Saudi cohort

Summary

Introduction

Pseudoexfoliation glaucoma (PXG) is an age-related and more aggressive form of open-angle glaucoma associated with a poor prognosis. PXG is characterized by excessive production and abnormal accumulation or deposition of pseudoexfoliative material, typically in the anterior segment of the eye that obstructs the aqueous flow pathway, leading to increased intraocular pressure (IOP), optic nerve head damage, retinal ganglion cell death (RGC), and subsequent loss of vision [1,2]. Genetic and environmental factors play an important role in the development and progression of the disease [3,4]. Previous genome-wide studies have identified genetic loci and polymorphisms associated with the disease phenotype [3,5,6]. The genetic factors and molecular mechanisms contributing to glaucomatous eye damage are still unclear. Increasing evidence suggests the critical roles of microRNA (miRNA) in glaucoma [7,8]

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