Analysis of the polymorphic variants of RAN and GEMIN3 genes and risk of Primary Open-Angle Glaucoma in the Polish population.

BACKGROUND: Glaucoma is considered as a neurodegenerative disorder in which the optic nerve damage leads to irreversible blindness. Many scientific findings indicate miRNA implication in the neurodegeneration process. In this study, we aimed to evaluate the polymorphic variants of miRNA processing genes, RAN (rs14035) and GEMIN3 (rs197388), and their association with a risk of primary open-angle glaucoma (POAG) in relation to selected clinical parameters. MATERIALS AND METHODS: The study included 246 POAG patients and 188 controls. The selected gene polymorphisms were analyzed by TaqMan SNP Genotyping Assay using DNA extracted from blood samples. RESULTS: The obtained results indicated that the AA genotype of rs197388 as well as the A allele in the same gene may be associated with an elevated risk of POAG development (P = 0.021, P = 0.017 respectively). The correlation between the data and clinical parameters has shown that the A allele of rs197388 in relation to retinal nerve fiber layer(RNFL) could be responsible for an increased risk of glaucoma occurrence (P = 0.028), while the AT genotype could be associated with a decreased risk of POAG according to the mean deviation parameter (P = 0.023). CONCLUSION: Our data has shown that GEMIN3 gene (rs197388) polymorphisms might be associated with a risk of POAG development in the Polish population. This is the first report evaluating the polymorphic variants of miRNA processing genes, RAN and GEMIN3, with a changed risk of glaucoma.

MicroRNAs in glaucoma and neurodegenerative diseases.

MicroRNAs (miRNAs) constitute a class of short, non-coding RNAs, which have important role in post-transcriptional regulation of genes expression by base-pairing with their target messenger RNA (mRNA). In recent years, miRNAs biogenesis, gene silencing mechanism and implication in various diseases have been thoroughly investigated. Many scientific findings indicate the altered expression of specific miRNA in the brains of patients affected by neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease and Huntington disease. The progressive optic nerve neuropathy associated with changed miRNA profile was also observed during glaucoma development. This suggests that the miRNAs may have a crucial role in these disorders, contributing to the neuronal cell death. A better understanding of molecular mechanism of these disorders will open a new potential way of ND treatment. In this review, the miRNAs role in particular neurodegenerative disorders and their possible application in medicine was discussed.

The analysis of single nucleotide polymorphisms of the DGCR8 and XPO5 genes, and their association with the incidence of primary open angle glaucoma. / Analiza polimorfizmów pojedynczych nukleotydów genów DGCR8 i XPO5 oraz ich zwiazek z wystepowaniem jaskry pierwotnej otwartego kata.

Purpose: To analyse the single nucleotide polymorphisms of DGCR8 and XPO5 genes, involved in miRNA processing pathway, in relation to the incidence of primary open-angle glaucoma. Material and methods: Blood samples as the biological material used for the experiment were voluntarily donated by patients with known primary open-angle glaucoma and age-matched healthy controls. The two control groups ­ rs3757 DGCR8 and rs11077 XPO5 ­ consisted of 135 and 140 volunteers, respectively. The two study groups ­ rs3757 DGCR8 and rs11077 XPO5 ­ consisted of 137 and 138 subjects, respectively. The polymorphic variant frequencies of rs3757 and rs1107 were determined using DNA isolated from the peripheral blood lymphocytes in TaqMan® SNP Genotyping Assays. Results: The statistical analysis revealed that the genotype AG of DGCR8 rs3757 occurred more frequently in healthy individuals (P = 0.001), while homozygote GG was present mostly in people affected by primary open-angle glaucoma (P = 0.003). No association between the risk of primary open angle glaucoma and AC/CC genotypes of XPO5 was found. Conclusions: Many reports suggest the association between the miRNA alteration and the pathogenesis of glaucoma. The single nucleotide polymorphisms in DGCR8 and XPO5 genes, involved in microRNA biogenesis, may be the key factor in this process. Our experiment showed that genotype AG in rs3757 DGCR8 exhibits protective effect, decreasing the risk of primary open angle glaucoma, while the homozygote GG is probably associated with increased risk of glaucoma. The analysis of polymorphic variants of the genes involved in miRNA biogenesis could enable identification of glaucoma high-risk groups.