- This study used data from two genome-wide association studies to examine whether APOE alleles are associated with primary open-angle glaucoma
- The APOE e4 allele, the strongest known genetic risk factor for Alzheimer's disease, was associated with reduced risk of primary open-angle glaucoma (OR, 0.83; 95% CI, 0.74–0.94; P=0.002)
- These findings imply a mechanistic difference between neurodegenerative diseases of the eye and those of the brain
Prior research has demonstrated that some of the genes associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis, also increase the risk of glaucoma—a group of disorders resulting in loss of retinal and optic nerve cells that is the third leading cause of blindness worldwide. However, Milica A. Margeta, MD, PhD, assistant professor of Ophthalmology at Harvard Medical School, and Janey L. Wiggs, MD, PhD, Paul Austin Chandler professor of Ophthalmology at Harvard Medical School and associate chief of Ophthalmology Clinical Research at Massachusetts Eye and Ear, and colleagues have found this isn't true across the board.
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In Investigative Ophthalmology & Visual Science, the researchers report that the apolipoprotein E (APOE) ε4 allele, the strongest known genetic risk factor for late-onset Alzheimer's disease (AD), is associated with reduced risk of primary open-angle glaucoma (POAG). This finding suggests a mechanistic difference between neurodegenerative diseases of the eye and brain.
The researchers analyzed data from two case–control genome-wide association studies:
- The Mass Eye and Ear component of the Glaucoma Genes and Environment study—486 POAG cases and 344 controls
- The National Eye Institute Glaucoma Human Genetics Collaboration—2,120 POAG cases and 2,262 controls
The team tested the following for their associations with glaucoma:
- APOE ε3, the most common APOE allele and considered the baseline for AD risk
- APOE ε4, which raises the risk of AD relative to ε3
- APOE ε2, which is protective against AD
In the combined dataset, APOE ε4 was inversely associated with POAG overall, and in both the high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) subgroups:
- POAG overall—OR, 0.83; 95% CI, 0.74–0.94; P=0.002
- HTG—OR, 0.81; 95% CI, 0.70–0.94; P=0.005
- NTG—OR, 0.71; 95% CI, 0.58–0.87; P=0.001
The largest effect of APOE genotype was observed for NTG cases versus controls (P=0.008). This implies that APOE could directly regulate retinal ganglion cell degeneration rather than indirectly through regulation of intraocular pressure.
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