Scientists have identified six genetic variants associated with the eye condition glaucoma in people from around the world including Australia.
The discovery, in three major studies, could help identify people at higher risk of the disease and lead to earlier screening and treatments.
All three studies, published today in Nature Genetics, identify gene sequence variations of the ABCA1 gene, which is involved in the regulation of cellular cholesterol and lipid metabolism, as playing a role in the eye disease.
Professor Jamie Craig, of the South Australian Health and Medical Research Institute and joint leader of the Australian project, says the finding is significant.
“It’s rock solid that this is an important result because it has been found in three different ways,” says Craig, who is also from Flinders University’s Centre for Ophthalmology and Eye Vision Research.
“All the papers were done in different populations with different strategies and all identified the same gene.
“It has been shown to be involved in eye pressure in normal people and tells us for sure it is contributing to glaucoma at least partly through intraocular pressure pathways.”
Glaucoma is the leading cause of irreversible blindness in the world.
It is caused by damage to the optic nerve, usually, but not always due to the eye pressure inside the eye (intraocular pressure) being too high, as the eye fluid does not drain properly.
People with a close relative with the disease are about 10 times more likely to contract the condition.
Early diagnosis of glaucoma is crucial because, if treated early enough, damage to vision can be prevented, says Craig.
Trio of studies
The Australian study, which also involved US researchers who replicated the findings, looked at potential gene targets in primary open-angle glaucoma (POAG).
POAG is the most common type of glaucoma and involves the progressive loss of peripheral vision until the central vision is affected.
The study included a cohort of 1155 patients from the Australian and New Zealand Registry of Advanced Glaucoma with severe POAG, and 1992 matched controls.
Genetic testing identified variants of three genes, ABCA1, AFAP1 and GMDS, which significantly increased the risk in Australians and Americans of European descent.
A second UK-led study, of which Craig is a co-author, involved genetic screening of 35,296 subjects including people with Asian and European descents drawn from across seven countries.
They found four new genes associated with high eye pressure and glaucoma. One of the genes is the ABO gene, which determines blood group, and higher eye pressure appears to be linked to blood group B.
The study also found a genetic change in the ABCA1 gene is associated with an increased risk of developing both high eye pressure and glaucoma.
The third Chinese study is unique says Craig because it is the first large-scale study of POAG in an Asian population.
It identified variants near two genes — ABCA1 and PMM2 — which are associated with glaucoma risk in people from China and Singapore.
Craig says the findings may in the future be used to develop risk profiles that will allow doctors to know whether a person has high-risk of their glaucoma being severe.
“We are looking at ways to add up a genetic risk profile,” says Craig. “So if you can say if you’ve got a larger load of these variant genes, your risk is high.”
Craig says the ageing population means there is a “potential tsunami of people beyond 90 now going blind in the last years of their life”.
“Sometimes it is the one thing that means they can’t live independently.”
He says if you can identify those people at high-risk of severe glaucoma it can be treated more aggressively early in their life to save their sight.
However, he cautions it will take several years of experiments before the exact role of the genes identified in these studies is known, and these steps need to be taken before new treatment strategies can be planned.