Sean Mullany, Henry Marshall, Puya Gharahkhani, Mark M. Hassall, Lachlan S. W. Knight1, Ella C. Berry1, Georgina Hollitt, Thi Nguyen, Angela Schulz, Richard A. Mills, Ashish Agar, Anna Galanopoulos, John Landers, Paul R. Healey, Stuart Graham, Alex W. Hewitt7, Robert Casson, Owen M. Siggs1,, Jamie E. Craig
Purpose: Due to conflicting evidence from epidemiological studies, it remains unclear whether the common dementia-associated apolipoprotein E (APOE) E4 allele is associated with primary open-angle glaucoma. This study seeks to investigate associations between APOE E4 allele prevalence and longitudinal spectral domain optical coherence tomography change in participants recruited to PROGRESSA, a prospective longitudinal study of suspect and early-manifest glaucoma.
Methods: APOE genotypes were imputed for 1206 individuals from PROGRESSA for whom genotyping data was available. Rates of longitudinal change in the macular ganglion cell layer/inner plexiform layer (mGCIPL) and peripapillary retinal nerve fibre layer (pRNFL) were compared between eyes of participants harbouring at least one copy of the E4 allele and participants lacking the E4 allele. Statistical comparisons were made between groups with adjustment for age and gender.
Results: Eyes of participants harbouring at least one copy of the APOE E4 allele demonstrated faster rates of mGCIPL thinning (β = 0.11μm/year; p = 2 x 10-4) but equivalent baseline mGCIPL thickness (β = -0.64μm; p = 0.12). These differences were not observed in longitudinal pRNFL thinning (β = 0.07μm/year; p = 0.12) nor baseline mean pRNFL thickness (β = -0.94μm; p = 0.12).
Conclusion: The APOE E4 allele is associated with faster rates of mGCIPL thinning in the PROGRESSA cohort. These data suggest that the APOE E4 genotype may be a relevant genetic risk factor for mGCIPL thinning and primary open-angle glaucoma disease progression
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