更年期及其与载脂蛋白E4等位基因在青光眼诊断中的作用

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-01-31 DOI:10.1016/j.xops.2025.100726

Yan Shi MD, PhD , William Liu , Junming Hu PhD , Wei Qiao Qiu MD, PhD , Xinyue He MD, PhD , Yan Gao MD , Xiaoling Zhang MD, PhD , Zhigang Fan MD, PhD

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引用次数: 0

摘要

目的探讨更年期对女性青光眼诊断年龄（AAD）的影响，并阐明其与载脂蛋白E (APOE) E4等位基因的相互作用。设计一项回顾性、仅病例分析，使用英国生物银行参与者的完整数据（2006-2010）进行分析。参与者：1358名女性青光眼患者。方法采用线性混合模型（LMM）分析青光眼AAD、APOE E4等位基因、绝经年龄和激素替代治疗（HRT）的多变量调整相关性，并按青光眼是在绝经前还是绝经后发生以及是否使用HRT进行分层。主要观察指标青光眼诊断年龄、绝经年龄、APOE E4等位基因、HRT信息。结果经年龄调整的单变量LMM显示，在整个队列和青光眼在绝经前或绝经后发生的亚组中，较晚的更年期与青光眼的老年AAD显著相关(模型1，所有P <；0.05)。经年龄调整的多因素LMM分析发现，携带APOE E4等位基因合并绝经后，绝经前诊断的青光眼患者的AAD显著增加(模型3:β绝经年龄= 0.711±0.074,P <；0.001;βe4 = 1.406±0.596,P = 0.019；模型1与模型3:P = 0.018)。在绝经后诊断的患者中未观察到类似的关联(P >；0.05)。此外，经年龄调整的单变量LMM显示，HRT与青光眼的老年AAD相关（模型4:βHRT = 1.239±0.368,P = 0.001），这种影响在绝经后期患者中更为明显(模型5:βHRT = 1.625±0.356,P <；0.001;绝经期β年龄= 0.301±0.033,P <；0.001;模型4 vs.模型5:P <；0.001)。结论：绝经后期与青光眼的老年AAD相关，APOE E4等位基因对绝经前诊断的青光眼的保护作用增强，而绝经后诊断的青光眼则没有。绝经后使用激素替代疗法也增强了绝经后的保护作用。这些发现强调了激素状态和APOE基因型在青光眼发病中的相互作用，可能指导青光眼和其他与年龄相关的女性健康状况的预防或管理。财务披露作者在本文中讨论的任何材料中没有专有或商业利益。

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The Role of Menopause and Its Association with the Apolipoprotein E4 Allele for Age at Diagnosis of Glaucoma in Women

Objective

To explore the impact of menopause for age at diagnosis (AAD) of glaucoma in women and illustrate its interaction with the apolipoprotein E (APOE) E4 allele.

Design

A retrospective, case-only analysis using the UK Biobank participants with complete data (2006–2010) for analysis.

Participants

One thousand three hundred fifty-eight female glaucoma patients.

Methods

Multivariable-adjusted associations of AAD of glaucoma, APOE E4 allele, age of menopause, and hormone replacement therapy (HRT) were analyzed by linear mixed model (LMM) analyses across groups stratified by whether glaucoma developed before or after menopause and whether or not HRT was used.

Main Outcome Measures

Age at diagnosis of glaucoma, age of menopause, APOE E4 allele, and HRT information.

Results

The age-adjusted univariate LMM showed that later menopause was significantly associated with an older AAD of glaucoma in both the overall cohort and subgroups where glaucoma developed before or after menopause (model 1, all P < 0.05). The age-adjusted multivariate LMM found that carrying the APOE E4 allele combined with later menopause significantly increased the AAD of glaucoma in patients diagnosed before menopause (model 3: β_{age of menopause} = 0.711 ± 0.074, P < 0.001; β_e4 = 1.406 ± 0.596, P = 0.019; model 1 vs. model 3: P = 0.018). No similar association was observed in patients diagnosed after menopause (P > 0.05). Additionally, the age-adjusted univariate LMM showed that HRT was associated with an older AAD of glaucoma (model 4: β_HRT = 1.239 ± 0.368, P = 0.001), with this effect being more pronounced in patients with later menopause (model 5: β_HRT = 1.625 ± 0.356, P < 0.001; β_{age of menopause} = 0.301 ± 0.033, P < 0.001; model 4 vs. model 5: P < 0.001).

Conclusions

Later menopause was associated with an older AAD of glaucoma, with the APOE E4 allele providing increased protection against glaucoma in those diagnosed before, but not after, menopause. The protective effect of later menopause was also enhanced by HRT use after menopause. These findings underscore the interaction of hormonal status and APOE genotype in glaucoma onset, potentially guiding the prevention or management of glaucoma and other age-related health conditions in women.