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Genetics of primary angle-closure glaucoma: genes and mechanisms

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Primary angle-closure glaucoma (PACG) is a disease with significant hereditability. It is characterized by glaucomatous optic neuropathy in the presence of closure of the angle between the iris and trabecular meshwork (the iridocorneal angle) and is a major cause of blindness worldwide. A greater risk of disease in first-degree relatives of PACG patients compared to the general population and a high heritability associated with angle-closure related ocular risk factors support a genetic basis for PACG. Candidate gene studies, based on modest case control cohorts, identified several plausible genes and a recent meta-analysis implicated five of these genes (HGF, HSP70, MFRP, MMP9 and NOS3) to be likely associated with PACG. Large-scale genome-wide association studies have been more successful and have to date identified eight genes or loci associated with PACG. These findings confirm PACG to be a complex disorder underpinned by the action of a large number of genetic variants of small effect sizes. The thus far identified PACG associated genes are involved in extracellular matrix remodeling (COL11A1, MMP9, NOS3, HSP70 and FERMT2), cellular adhesion (PLEKHA7, FERMT2 and EPRD1), and ocular development (MFRP, PRSS56, and ABCC5). Identification and functional characterization of the causal variants at the associated genetic loci will allow better understanding of the alluded pathways and mechanisms for PACG in the future. This chapter summarizes the current status of genetic investigations on PACG.

Glaucoma Research 2018-2020, pp. 113-126 #8
Edited by: John R. Samples and Paul A. Knepper
© Kugler Publications, Amsterdam, The Netherlands

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