Common variants may be behind the risk of developing glaucoma, according to University of California, San Diego's Kang Zhang. Currently, risk factors for glaucoma include a person's intraocular pressure, ethnicity, and a family history of the disease. The prevalence of glaucoma in people of African ancestry is about 2 percent to 5 percent, higher than the 1 percent to 2 percent reported among Caucasians. However, the rate is even higher among Afro-Caribbeans, reaching about 10 percent. To search for gene variants behind this disease, Zhang teamed up with researchers involved with the Barbados Family Study.
"There is a strong genetic influence of glaucoma in [the] Barbados population. That was the impetus for us to look through the human genome to actually see if there are gene variants which play a major role and have a high impact on glaucoma risk," Zhang says.
Building on previous studies that identified a region associated with primary open angle glaucoma, Zhang and his colleagues performed a whole-genome linkage scan of 146 families from Barbados with at least three members with glaucoma and controls. That work was then followed by focused genotyping. Through that they homed in on a section of chromosome two, 2q16. Their finding fits with previous results: 2q16 overlaps with an area linked to monogenic open angle glaucoma. Being homozygous for this variant, Zhang says, would lead to a 30-fold increased chance of having glaucoma, as they report in PNAS.
"To my knowledge this is the first common variant [for glaucoma]," Zhang says. "This, once verified, is going to be one of the first major genes affecting glaucoma risk."
In glaucoma, Zhang says, ganglion cells die, leading to vision loss. "We don't understand why those cells are dying," he says, adding that anything dealing with synapse formation could be involved in the pathogenesis of the disease. Though the region the researchers identified does not contain any known genes, there are a few located nearby, including neurexin, which is linked to synapse formation and transmission. Zhang and his colleagues are following up on that gene.
Of course, Zhang says, the study must be replicated and the findings verified. If that happens, "then this can serve as a marker for genetic testing and to identify pre-symptomatic patients, so we can intervene to slow down the progression and hopefully find a cure for glaucoma," he says.