Inverse Association of APOE ε4 and Glaucoma Modified by Systemic Hypertension: The Canadian Longitudinal Study on Aging

PURPOSE: Studies examining the apolipoprotein E (APOE) ε4 allele and glaucoma are inconsistent, which could be due to interactions with other factors. We examined the relationship between the APOE ε4 allele and glaucoma and intraocular pressure in a large, population-based random sample and explored whether the APOE ε4 allele interacted with systemic hypertension. METHODS: Data came from the Canadian Longitudinal Study on Aging, a population-based study that included 24,655 adults ages 45 to 85 years old in the European ancestry cohort. APOE genotypes were derived from single-nucleotide polymorphisms rs429358 and rs7412. Participants were asked about a prior diagnosis of glaucoma from a doctor. Corneal compensated intraocular pressure (IOP) was measured using the Reichart Ocular Response Analyzer. RESULTS: Having an APOE ε4 allele was associated with a lower odds of glaucoma after adjusting for age, sex, IOP, and the top 10 population structure principal components (odds ratio [OR] = 0.83; 95% confidence interval [CI], 0.69-0.98; P = 0.033). A novel statistically significant interaction was found in that having an APOE ε4 allele was only associated with glaucoma in those without systemic hypertension (OR = 0.62; 95% CI, 0.46-0.85) although it was not associated in those with it (OR = 0.97; 95% CI, 0.79-1.21) (interaction term P value = 0.017). APOE ε4 was not associated with IOP (β = −0.01; 95% CI, −0.13 to 0.10). CONCLUSIONS: Evidence increasingly points to the APOE ε4 allele having protective benefits against glaucoma, but this association was limited to those without systemic hypertension. Further research is needed to understand the biological mechanisms for these findings and the treatment potential they hold.