Scientists Discover A Mutation That Prevents Glaucoma

Although other variants of the LOXL1 gene have been linked to glaucoma, the p.Y407F mutation offers a 25-fold protection against the disease.

AsianScientist (July 17, 2017) – In the largest study on any cause of glaucoma to date, researchers have found a mutated gene that can prevent glaucoma, the leading cause of irreversible blindness worldwide. These findings have been published in Nature Genetics.

Jointly led by the Agency for Science, Technology and Research’s (A*STAR) Genome Institute of Singapore (GIS) and the Singapore Eye Research Institute (SERI) of the Singapore National Eye Centre (SNEC), the study involved more than 120,000 individuals from 36 countries across six continents.

Exfoliation syndrome (XFS) is an age-related eye disease where abnormal whitish flakes are deposited in the front of the eye and abnormalities in connective tissues may appear in parts of the body. The disease occurs globally in approximately 60 to 70 million people. In the eye, the disease often leads to an increase in eye pressure, or glaucoma, which can result in visual impairment and blindness.

In 2007, an Icelandic study found that common genetic variations in the LOXL1 gene show a strong association with XFS. However, the association with common genetic markers at LOXL1 are reversed depending on ethnic group, thus rendering the health implications unclear.

In this latest study, the researchers uncovered a rare protective mutation in the LOXL1 gene. The mutation, p.Y407F, was found to offer protection against XFS instead, thereby leading to the prevention of secondary glaucoma. The mutation offers a 25-fold protection against XFS, the largest ever seen for a common, complex disease.

“Naturally occurring genetic variants are hard to find, but once discovered, they pinpoint potential druggable targets. These are what we call ‘accidents and experiments of nature’. The LOXL1 p.Y407F rare variant reported in this study is one of these examples,” explained Dr. Khor Chiea Chuen, one of the study’s corresponding authors and Principal Investigator of Human Genetics at the GIS.

In addition, the researchers also discovered five new susceptibility gene loci in XFS, specifically POMP, TMEM136, AGPAT1, RBMS3 and SEMA6A. This will help deepen the researchers’ understanding of XFS and how the disease process works.

“This is a truly remarkable study that demonstrates the power of international collaboration. The results improve our understanding of glaucoma and also suggest important new therapeutic strategies for this common cause of blindness,” said study joint corresponding author Professor Janey L. Wiggs, who holds the post of Paul Austin Chandler Professor of Ophthalmology at the Harvard Medical School.

Glaucoma is the commonest cause of blindness amongst the elderly; understanding how this process happens will result in new medications to cure it.

The article can be found at: Aung et al. (2017) Genetic Association Study of Exfoliation Syndrome Identifies a Protective Rare Variant at LOXL1 and Five New Susceptibility Loci.


Source: A*STAR; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Asian Scientist Magazine is an award-winning science and technology magazine that highlights R&D news stories from Asia to a global audience. The magazine is published by Singapore-headquartered Wildtype Media Group.

Related Stories from Asian Scientist