Polymorphism analysis of miR182 and CDKN2B genes in Greek patients with primary open angle glaucoma

Abstract

Glaucoma is a progressive optic neuropathy resulting from retinal ganglion cells death; it represents one of the leading causes of irreversible blindness worldwide. Although, primary open angle glaucoma (POAG) is the most common type of the disease, the pathogenesis of POAG and the genetic factors contributing to disease development remain poorly understood. The aim of this study was to investigate whether the polymorphisms rs76481776 in miR182 gene and rs3217992 in cyclin-dependent kinase inhibitor-2B (CDKN2B) gene are risk factors for POAG in a series of patients of Greek origin. A case-control study was conducted including 120 patients with POAG and 113 unaffected healthy controls of Greek origin, surveyed for polymorphisms with potential correlation to POAG. DNA from each individual was tested for the miR182 rs76481776 and CDKN2B rs3217992 polymorphisms. Regarding the miR182 rs76481776 polymorphism, the T allele occurred with significantly higher frequency in POAG patients compared to controls (OR: 2.62, 95% CI: 1.56-4.39; p = 0.0002). The CDKN2B rs3217992 A allele frequency was found significantly increased in POAG patients compared to healthy individuals (OR: 1.72, 95% CI: 1.18-2.49; p = 0.005). Therefore, both rs76481776 polymorphism in miR182 gene and rs3217992 polymorphism in CDKN2B gene seem to be associated with the development of POAG in a Greek population. The carriers of the T allele of rs76481776 in miR182 and the carriers of the A allele of rs3217992 in CDKN2B have an increased risk of developing POAG.

The haplotype of the CDKN2B-AS1 gene is associated with primary open-angle glaucoma and pseudoexfoliation glaucoma in the Caucasian population of Central Russia

“…It should be noted that, while numerous works have reported the association of this gene with normaltension POAG in European, African Americans, Australians, and Chinese populations (11,35,36,49,50, etc. ), some studies showed a relationship between CDKN2B-AS1 gene polymorphisms and high-tension POAG in different ethnic populations (37,51). Specifically, several SNPs of the CDKN2B-AS1 gene were associated with high-tension POAG (IOP > 21 mm Hg) in the North Indian Punjabi (51) and Greek (37) populations.…”

Alternate Causes for Pathogenesis of Exfoliation Glaucoma, a Multifactorial Elastotic Disorder: A Literature Review

“…It is believed that concentrating on the polymorphisms in the miRNA biogenesis pathway and their dynamic interaction with the genes under specific environmental triggers could uncover data for disease anticipation and pharmacogenomics in XFS [44][45][46]. Recently, various studies have reported differential miRNA expression status in the AH and trabecular meshwork, two anatomical structures that are closely related to glaucoma, and linked them to the apoptosis of retinal ganglion cells and IOP [21,38,39].…”

“…Recently, various studies have reported differential miRNA expression status in the AH and trabecular meshwork, two anatomical structures that are closely related to glaucoma, and linked them to the apoptosis of retinal ganglion cells and IOP [21,38,39]. Fewer studies, however, have reported polymorphisms in miRNA [45][46][47][48]. One study reported rs1057035 polymorphisms in the 3 -UTR of the DICER gene to be associated with a decreased risk of XFG, and rs55671916 in the 3 -UTR of the exportin 5 (XPO5) gene with an increased risk of XFG [4,47].…”

The Role of MicroRNAs in Mitochondria-Mediated Eye Diseases

“…In particular, miR-182 was found to be the most abundant miRNA also in the axons of developing RGC where it regulates axon guidance (Bellon et al, 2017). Interestingly, a case-control study conducted on patients with primary open-angle glaucoma (POAG) concludes that the carriers of polymorphism in miR-182 and CDKN2B genes have an increased risk of developing POAG (Moschos et al, 2020). MiR-204 caused reduced expression of FOXC1, implicated in glaucoma development, and its target genes (Paylakhi et al, 2013).…”