Purpose: To assess whether genetic polymorphisms of the apolipoprotein E (APOE) gene are associated with open angle glaucoma (OAG) in the Japanese population.
Methods: Genomic DNA was examined in a cohort of 310 Japanese patients with OAG and 179 control subjects. The average age was 63.5+/-14.4 years (mean+/-SD) for the OAG patients and 65.5+/-11.6 years for the control subjects. The presence or absence of OAG in patients and controls was based on clinical examination and/or ophthalmic records. The APOE allele frequency (epsilon2, epsilon3, and epsilon4 alleles) was studied by restriction fragment length polymorphism, and compared between OAG patients and control subjects. The association between the intraocular pressure (IOP) and the APOE alleles was also evaluated.
Results: There was a significant difference in the APOE genotype frequencies between these groups (p=0.0006 chi2 test). The frequencies of the epsilon2 and epsilon4 alleles were significantly lower in the OAG patients (epsilon2: 2.6%; epsilon4: 6.0%) compared to the control subjects (epsilon2: 5.0%, p=0.048; epsilon4: 10.6%, p=0.012; Fisher's exact test). The frequency of the epsilon3 allele was significantly higher in the OAG patients (91.4%) compared to the control subjects (84.4%, p=0.0010; Fisher's exact test). Adjusted for age, gender, and IOP, an appropriate three fold reduction in OAG risk (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.10 to 0.80; p=0.018) was found with the epsilon2 allele and a two fold increased risk of OAG (OR 1.97, 95% CI 1.06 to 3.67; p=0.033) was found with the epsilon3 allele. The maximum IOP (18.3+/-6.0 mm Hg) in patients with the epsilon4 allele was significantly lower than that (21.3+/-9.1 mm Hg) in patients without the epsilon4 allele (p=0.006, Student's t-test).
Conclusions: The APOE gene polymorphism is associated with OAG in the Japanese population. Further studies in the other ethnic populations should be performed to elucidate the relationship between APOE and OAG.