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Did you ever wonder ... what is LOXL1?
Study: Two DNA sequence changes in the gene for lysyl oxidase-like protein 1 indicated a higher risk of developing pseudoexfoliation glaucoma.
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Although not published in ophthalmology-specific journals, a collaborative group from Iceland and Sweden reported one of the most significant discoveries in glaucoma genetics this year in the journal Science.
They found that two single nucleotide polymorphisms (SNPs) in the gene for lysyl oxidase-like protein 1 (LOXL1) were associated with the development of pseudoexfoliation glaucoma (PXF) in a group of about 14,600 Icelanders. They wrote, “The risk of individuals carrying two copies of the high risk haplotype (G,G allelic change) would have about 700 times the risk of those carrying two copies of G,A and about 2.47-fold higher than the population average risk.”
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Does this mean that LOXL1 causes PXF? Probably not. Twenty-five percent of the population is homozygous for the high-risk SNPs. Not all people who have these alleles will develop glaucoma. However, those who do have a very high risk for PXF.
LOXL1 is one of a five-member family of enyzmes involved in the formation of elastin, which is a major component of extracellular matrix. Thus, it is possible that some alteration of elastogenesis greatly increases the susceptibility of developing PXF when a second physiologic/metabollic stressor occurs. Interestingly, transgenic mice that do not express LOXL1 (ie, “knock out” mice) have a much greater risk of choroidal neovascular membrane formation in response to argon laser disruption of Bruch’s membrane — ie, increased disease pathophysiology due to a secondary insult.
Well then, how is this relevant for my practice? At the moment, we can simply say that significant progress is being made toward genetic testing to better predict who will get glaucoma and how they will respond to treatment.
For more information:
- Douglas J. Rhee, MD, is an assistant professor of ophthalmology at Harvard Medical School and on the faculty of the Massachusetts Eye and Ear Infirmary. He can be reached at 243 Charles St., Boston, MA 02144; 617-573-3670; fax: 617-573-3707; e-mail: dougrhee@aol.com.
Reference:
- Thorleifsson G, Magnusson KP, et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science. 2007;317(5843):1397-1400.