Apolipoprotein E (APOE) Promoter SNPs Affect the Phenotype of Primary Open-angle Glaucoma and Demonstrate Interaction With the MYOCILIN Gene

Abstract

Abstract: : Purpose: To investigate a role of the apolipoprotein E (APOE) gene in predisposition to primary open-angle glaucoma (POAG). Methods: 191 patients with POAG and 102 control persons were genotyped for APOE protein alleles and for 3 APOE promoter single nucleotide polymorphisms (SNPs). Results: The frequencies of APOE polymorphisms were not different among patients and controls. However, two APOE promoter SNPs were found to modify the phenotype of POAG patients. APOE(-219T) was associated with greater optic nerve damage, as reflected by increased cup/disk ratio (P=0.01) and by visual-field alteration (P=0.001). Additionally, APOE(-491T), interacting at a highly significant level with a SNP in the MYOCILIN (MYOC) gene promoter, MYOC(-1000G), was associated with increased intra-ocular pressure (IOP) and poor IOP lowering in POAG patients (P<0.0001 by ANCOVA). Conclusion: The two APOE promoter SNPs were previously associated with Alzheimer’s disease and were also shown to influence APOE transcriptional activity. Our present findings establish APOE as a major candidate in POAG predisposition. They also shed new light on the mechanisms of optic nerve damage and of IOP regulation in POAG.

Keywords: 420 genetics • 444 intraocular pressure • 624 visual fields