[Analysis of the functional role of polymorphism in the CDKN2B-AS1 gene GWAS-significant for primary open-angle...

Primary open-angle glaucoma (POAG) is the most common form of glaucoma in which genetic factors play a significant role. According to genome-wide studies (GWAS), the CDKN2B-AS1 gene is associated with POAG.

To study in silico the functional significance of the CDKN2B-AS1 gene polymorphism GWAS-significant for primary open-angle glaucoma.

The in-silico analysis was based on data from the GWAS catalog, five polymorphic loci of the CDKN2B-AS1 gene (rs1063192, rs7865618, rs2157719, rs944800, rs4977756) associated with POAG were selected. The study evaluated the regulatory potential, the relationship with the expression and alternative splicing of genes of the CDKN2B-AS1 gene polymorphism using modern databases for functional genomics - HaploReg and GTExportal.

An important functional significance of the polymorphic loci rs1063192, rs7865618, rs2157719, rs944800, rs4977756 of the CDKN2B-AS1 gene was revealed. These loci are located in the region of histones marking enhancers and in the region of hypersensitivity to DNAse-1, can be found in more than ten different organs and tissues, in the regions of regulatory DNA motifs to five transcription factors (AIRE, GATA, Tgif1, Pou2f2, and Zfp187), and are associated with expression of three genes (CDKN2B-AS1, CDKN2B, CDKN2A) and alternative splicing of transcripts of two genes (CDKN2B-AS1 and RP11-149I2.4) in cell cultures, organs and tissues with pathogenic significance for glaucoma development.

Polymorphism of the CDKN2B-AS1 gene (rs1063192, rs7865618, rs2157719, rs944800, rs4977756) has significant regulatory potential and is associated with the expression and alternative splicing of genes, which possibly underlies its association with primary open-angle glaucoma.