Updates on Genes and Genetic Mechanisms Implicated in Primary Angle-Closure Glaucoma

Abstract

Primary angle-closure glaucoma (PACG) is estimated to affect over 30 million people worldwide by 2040 and is highly prevalent in the Asian population. PACG is more severe and carries three times the higher risk of blindness than primary open-angle glaucoma, thus representing a significant public health concern. High heritability and ethnic-specific predisposition to PACG suggest the involvement of genetic factors in disease development. In the recent past, genetic studies have led to the successful identification of several genes and loci associated with PACG across different ethnicities. The precise cellular and molecular roles of these multiple loci in the development and progression of PACG remains to be elucidated. Nonetheless, these studies have significantly increased our understanding of the emerging cellular processes and biological pathways that might provide more significant insights into the disease's genetic etiology and may be valuable for future clinical applications. This review aims to summarize and update the current knowledge of PACG genetics analysis research.

Keywords: GWAS; PACG; angle-closure; candidate genes; extracellular matrix; genetics; glaucoma; pathways; polymorphisms; trabecular meshwork.

Figure 1

Schematic representation of risk factors contributing to angle-closure in PACG. The curved arrow from the ciliary epithelium indicate the normal flow of aqueous humor in open-angle which is blocked in angle-closure.

Figure 2

Bar chart showing an overview of pathways significantly overrepresented by a set of genes identified in PACG using Enrichr online tool (https://maayanlab.cloud/Enrichr/). An asterisk (*) next to a p-value indicates the term also has a significant adjusted p-value (<0.05).