Primary open angle glaucoma (POAG) is a genetically complex disease and the overall phenotype is influenced by multiple traits including intraocular pressure (IOP), central corneal thickness and structural features of the optic nerve head. Therefore, genes affecting any of these are likely to influence the risk of developing POAG. Many genome wide association studies (GWASs) have been conducted and multiple genetic loci were found to be associated with POAG. However, chromosome 9p21 was the only locus to yield a consistently strong association in subsequent replication studies across different populations including Australians, Americans, Europeans, Japanese and Afro-Caribbeans. A particularly strong association was found between the risk alleles of CDKN2B/CDKN2B-AS (cyclin-dependent kinase inhibitor 2B and 2B antisense) on 9p21 to both high tension POAG and normal tension glaucoma (NTG), but there was a greater level of significance to the NTG group. It was postulated that carriers of the risk alleles are predisposed to glaucomatous optic neuropathy either in a way that is independent of IOP or via an increased vulnerability of the retinal ganglion cells to IOP, even at levels considered normal for most of the population. CDKN2B encodes for p15INK4b, which is an inhibitor of cyclin-dependent kinase 4 that plays an important role in the maintenance of cell cycle progression. This may consequently cause retinal ganglion cell apoptosis, however, the exact molecular mechanism linking the association between CDKN2B/CDKN2B-AS1 and POAG is unknown. The authors conclude that this discovery is still a work in progress and that further research is necessary to understand the pathogenetic molecular pathways linking POAG to 9p21.

Chromosome 9p21 primary open-angle glaucoma susceptibility locus: a review.
Ng SK, Casson RJ, Burdon KP, et al.
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Anjali Gupta

Birmingham and Midland Eye Centre, Birmingham, UK.

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