Female-Specific Association between the Apolipoprotein E E4 Allele and Age at Diagnosis of Glaucoma in UK Biobank

Abstract

ObjectiveTo explore the impact of the apolipoprotein E (APOE) E4 allele in the gender-specific aging process in glaucoma by illustrating the interaction between risk factors, including the APOE E4 allele, gender and intraocular pressure (IOP), for age at diagnosis (AAD) of glaucoma. DesignA cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis. Data were analyzed in December 2023. Participants2,236 glaucoma patients and 103,232 controls. MethodsWe evaluated multivariable-adjusted associations of AAD of glaucoma, APOE E4 allele (0: absence; 1: presence), and IOP using linear mixed model (LMM) analyses across groups stratified by AAD of mean age of menopause (50 years) and gender. Main Outcomes MeasuresAAD of glaucoma, APOE E4 allele and IOP. ResultsGlaucoma patients were older and had a higher percentage of males and a higher mean IOP compared to controls (all P < 0.001). Further stratifying the glaucoma patients by AAD of 50 and gender, lower IOP (Model 1 adjusted by age, βIOP=-0.096±0.041, P=0.019) and positive APOE E4 allele (Model 2 adjusted by age and IOP, βe4=1.093±0.488, P=0.026) were associated with an older AAD in females with an AAD < 50 years under univariate LMM. In multivariate LMM adjusted by age (Model 3), the effect size of both factors increased in the multivariate model as the beta-value increased. (βIOP=-0.111±0.040, P=0.007; βe4=1.235±0.485, P=0.012) (Model 1 vs Model 3: P=0.011). In females with an AAD ≥50 years, only positive APOE E4 allele (adjusted by age and IOP, βe4=-1.121±0.412, P=0.007) was associated with a younger AAD. In males, only higher IOP was associated with an older AAD in those with an AAD ≥50 years (βIOP=0.088±0.032, P=0.006). ConclusionsAPOE E4 allele may initially delay and later accelerate the development of glaucoma in females around the transition period of 50 years, which is the mean age of menopause, and importantly, this is independent of IOP. Understanding the specific transition states and modifiable factors within each age phase is crucial for developing interventions or strategies that promote healthy aging.