Work done by Dr Jessica Cooke Bailey of Case Western Reserve University School of Medicine and co-authors has led to the discovery of three genes that contribute to the most common type of glaucoma. The findings are published in the Jan. 11 online edition of the journal Nature Genetics.
The study increases the total number of POAG-related genes to 15. Image credit: National Eye Institute.
Glaucoma is a group of conditions that damage the optic nerve, the bundle of nerve fibers connecting the eye to the brain.
The most common type, primary open-angle glaucoma (POAG), is a leading cause of blindness worldwide.
Some rare types are inherited via a single gene. The underlying causes of POAG remain poorly understood, but likely involve the interaction of many genes with environmental influences.
Dr Cooke Bailey and her colleagues from the United States, UK, Australia, Singapore, Switzerland, Greece, and Germany, compared the DNA of 3,853 people of European ancestry with POAG to a similar group of 33,480 people without it.
The analysis showed that specific variations in the genes FOXC1, TXNRD2, and ATXN2 are associated with glaucoma.
All three genes are expressed in the eye. TXNRD2 and ATXN2 are active in the optic nerve.
Scientists had already identified an association between FOXC1 and glaucoma, but only in rare cases of severe early-onset glaucoma.
The TXNRD2 gene makes an enzyme that protects mitochondria against oxidative stress – the build-up of toxic byproducts from normal metabolism.
Mitochondria are energy-producing cellular components. For years, scientists have suspected that oxidative stress might contribute to the degeneration of the optic nerve, but until now they lacked evidence.
“This is the first direct report to show the association of a gene linking oxidative damage to glaucoma,” said Dr Neeraj Agarwal of the National Eye Institute, who was not involved in the study.
The study suggests that people with TXNRD2 gene variants may have a reduced ability to protect mitochondria from damage, leading to optic nerve cell death.
Little is known about the normal function of ATXN2. Mutations of the gene are implicated in a rare disorder called spinocerebellar ataxia 2 that causes loss of balance and coordination.
Interestingly, ATXN2 is the third gene associated with both glaucoma and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. However, there is no evidence that people with glaucoma are at greater risk of developing ALS.
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Jessica N. Cooke Bailey et al. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nature Genetics, published online January 11, 2016; doi: 10.1038/ng.3482
