Only One Gene for Exfoliative Glaucoma

by Dr. Hsien-Hsien Lei
Posted August 11, 2007 in DNA and Disease

Most common diseases like heart disease and diabetes are caused by more than one gene and are sometimes interchangeably called complex, polygenic diseases. But as this past week’s finding of the connection between exfoliative glaucoma and the lysyl oxidase-like 1 gene (LOXL1) shows, sometimes one gene is all it takes.

Exfoliative glaucoma is a common disease of aging. At least 10-20% of people after age 60 are affected to some degree by exfoliation syndrome. In Iceland and Finland (from where the researchers of this new study hail), exfoliative glaucoma rates are over 20% in persons over age 60. The build-up of extracellular material in the eye can lead to glaucoma and may also cause cataract, lens dislocation, and central retinal vein occlusion resulting in blindness. The causes of exfoliative glaucoma are not well understood.

Some of the major risk factors for glaucoma include:

• Age
• Family history
• Race - Blacks have a higher risk
• Diabetes
• Eye injury

In a recent genomewide association study of 16,000 Icelandic and Swedish participants, researchers from deCODE Genetics, the National University Hospital in Reykjavik and Uppsala University in Sweden found two single nucleotide polymorphisms (SNPs) on chromosome 15, single base differences in the sequence of the LOXL1 gene. Allele G of rs1048661 and allele G of rs3825942 accounted for 99% of all cases of exfoliative glaucoma. An estimated 25% of the general population is believed to have two copies of the high risk haplotype with a corresponding 100 times increased risk of developing the disease.

Kari Stefansson, CEO of deCODE:

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 [emphasis added]. 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.

And, of course, diagnostic DNA tests to identify high risk patients carrying these gene variants may also help with treatment and prevention.

New York Times, August 10, 2007
Science, August 9, 2007

Tags: lysyl oxidase-like 1 gene, LOXL1, exfoliative glaucoma, glaucoma, eye, diseases, medicine, genome, genomics, genetics, genes, dna, decode, kari stefansson

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3 Comments »

Pingback by » This week in health and science - 8/11/07 - Women's Health Research News blog from IdeasForWomen.com

2007-08-12 01:47:04

[...] Lei wrote about a disease associated with aging: exfoliative glaucoma and how it has been discovered that one gene - lysyl oxidase-like 1 (LOXL1) is responsible for it. [...]

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Comment by Tom

2007-11-03 17:18:31

Very interesting research on PXF (pseudoexfoliation glaucoma). If you are interested in seeing with this type of glaucoma looks like in vivo, you may be interested in seeing this microscope video:

Exfoliation glaucoma of the eye

Amazing that this phenotype has been linked to a single gene.

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Pingback by deCODE CEO Predicts Dowswing in Personal Genomics Market

2008-03-05 13:23:10

[...] deCODE Glaucoma - A genetic test for exfoliation glaucoma that detects SNPs located in the LOXL1 gene on chromosome 15. (For more, see this Eye on DNA post.) [...]

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