Two Risk Genes Interact to Cause Primary Open-Angle Glaucoma

by: a GenomeWeb staff reporter

NEW YORK (GenomeWeb) – Two risk genes interact to cause the development of primary open-angle glaucoma, according to a new study from researchers at the University of California, San Diego.

Primary open-angle glaucoma, one of the leading causes of blindness in Western countries and the leading cause among African Americans, is marked by increased intraocular pressure and the slow, progressive degeneration of retinal ganglion cells.

Through a combination of genetic association and functional studies, UCSD’s Kang Zhang and his colleagues found that a SIX6 risk variant increases the expression of p16INK4a, another risk gene, and leads to the senescence of retinal ganglion cells. These findings, which were reported in Molecular Cell today, could lead to new treatments for glaucoma, the researchers said.

“Glaucoma is currently treated by lowering intraocular pressure; however, lowering IOP can only slow down progression — it does not prevent retinal ganglion cell death and blindness,” Zhang said in a statement. “Inhibiting [the risk gene product] P16 can be an important drug target for treatment of glaucoma.”

Through genetic association studies, the researchers found that a missense variant in SIX6 is strongly associated with primary open-angle glaucoma. In addition, they reported that this variant was more common among patients than controls in a Caucasian cohort of 1,130 glaucoma patients and 4,306 controls, as well as in a Mexican replication cohort.

SIX6, they added, is part of the SIX/Sine oculis family of homeobox transcription factors that are involved in retinal development.

The p16INK4a gene also exhibited a strong association with glaucoma risk, and together, variants in the two genes increase the risk of developing glaucoma some 2.7 times, the researchers reported.

Using RT-qPCR, theyfound that human lymphoblastoid cells carrying the SIX6 risk allele had higher expression levels of SIX6 and p16INK4a mRNA, 1.4-fold and 2.3-fold, respectively………


Source: genomeweb