Icelandic and Swedish scientists have discovered two common single letter variations (SNPs) in the sequence of the human genome that appear to account for 99 per cent of cases of exfoliative glaucoma (XFG). The scientists from deCODE genetics and colleagues from the National University Hospital in Rekjavik and Uppsala University in Sweden reported that the SNPs are located in the lysyl oxidase-like 1 gene (LOX1) on chromosome 15. This finding offers hope for more efficient diagnosis and treatment of the condition.
The deCODE team began their work with an analysis of over 300,000 SNPs using recently developed DNA scanning chips. By comparing patients and control subjects researchers were able to determine which sites are associated with the disease. Kari Stefansson, CEO of deCODE, and colleagues discovered two risk variants in the LOX1 gene that are strongly linked to XFG; these SNPs confer increased risk of 26-fold and 8-fold compared to the low risk versions of the same markers. Over 16,000 Icelandic and Swedish patients and controls took part in the study.
The LOX1 protein encoded by the gene is produced in many tissues of the body, including the eye, and is involved in cross-linking elastin fibres. The effect of the genetic variants seems to be to lower the production rate of this protein. In XFG, microfibullar deposits build on the surfaces on the front of the eye, increasing fluid pressure that gradually damages the optic nerve, leading to a progressive loss of vision. The variants are very common and the production rate is only slightly lowered; it therefore appears to matter little in the early and middle ages of life. Exfoliative glaucoma is most common among the elderly, as the deficit may accumulate through the decades. Between 10 and 20 percent of people over 60 have an accumulation of flaked off fibres in the eye, and half of these will go on to develop glaucoma.
According to Stefansson, DeCODE genetics is also developing a test to enhance the efficiency of diagnosis and hopes to have it on the market 'before the end of this year'. Exfoliative glaucoma is a particularly difficult form of glaucoma to treat; it is often resistant to drug treatment. Early diagnosis could alert the physician to the possible need for surgical intervention.
This finding, reported in the journal Science, 'is remarkable and important', according to Stefansson, who added: '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'. The researchers believe that this gene will provide a 'promising mechanism to target for developing therapy' and intend to carry out additional studies to examine the possibility of drug treatment.