In a paper published in the journal Science, scientists from deCODE genetics and academic colleagues from the National University Hospital in Reykjavik and Uppsala University in Sweden report the discovery of two common single letter variations (SNPs) in the sequence of the human genome that appear to account for virtually all cases of a major subtype of glaucoma.
The SNPs are located in the LOXL1 gene on chromosome 15, and confer respectively 26-fold and 8-fold increases in risk of exfoliation glaucoma compared to the low-risk versions of the same markers.
Approximately 25% of those in the Icelandic and Swedish study cohorts were found to have two copies of the highest risk variant, putting them at approximately 100 times the likelihood of developing exfoliation glaucoma (XFG) as are individuals with the low risk version of the same SNP.
The LOXL1 protein encoded by the gene is involved in the formation of elastin fibers which, when they accumulate in the eye, cause XFG.
The paper, entitled “Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma,” is published in the online edition of Science, and will appear in an upcoming print edition of the journal.
“This discovery is remarkable and important because the genetics has led us directly to what appears to be the sole cause of a devastating common disease. The risk conferred by these variants is such that it accounts for virtually all cases of exfoliation glaucoma, meaning that if we can neutralize the impact of these variants we might eliminate the disease,” said Kari Stefansson, CEO of deCODE.
Stefansson continued, “The LOXL1 protein made by this gene appears to play a role in the accumulation of microfibullar deposits that causes XFG, providing a promising mechanism to target for developing therapy. We plan to conduct additional studies to examine how we can take advantage of this finding to begin drug discovery.”