Mullany Sean, Diaz-Torres Santiago, Schmidt Joshua M, Thomson Daniel, Qassim Ayub, Marshall Henry N, Knight Lachlan S W, Berry Ella C, Kolovos Antonia, Dimasi David, Lake Stewart, Mills Richard A, Landers John, Mitchell Paul, Healey Paul R, Commerford Toby, Klebe Sonja, Souzeau Emmanuelle, Hassall Mark M, MacGregor Stuart, Gharahkhani Puya, Siggs Owen M, Craig Jamie E
Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia.
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Ophthalmol Sci. 2023 Feb 13;3(3):100287. doi: 10.1016/j.xops.2023.100287. eCollection 2023 Sep.
To elucidate a potential association between the apolipoprotein E () E4 allele and glaucoma prevalence in large cohorts.
A cross-sectional analysis of baseline and prospectively collected cohort data.
UK Biobank (UKBB) participants of genetically determined European ancestry (n = 438 711). Replication analyses were performed using clinical and genotyping data collected from European participants recruited to the Canadian Longitudinal Study of Aging (CLSA; n = 18 199), the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG; n = 1970), and the Blue Mountains Eye Study (BMES; n = 2440).
Apolipoprotein E alleles and genotypes were determined, and their distributions were compared on the basis of glaucoma status. Similar analyses were performed using positive control outcomes associated with the E4 allele (death, dementia, age-related macular degeneration) and negative control outcomes not associated with the E4 allele (cataract, diabetic eye disease). Outcome phenotypes were also correlated with Alzheimer's dementia (AD), a clinical outcome highly associated with the E4 allele.
Results of E4 genotype-phenotype comparisons were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Replication analyses investigated E4 associations in 2 replication cohorts (CLSA and ANZRAG/BMES).
The E4 allele was inversely associated with glaucoma (OR, 0.96; 95% CI, 0.93-0.99; = 0.016) and both negative controls (cataract: OR, 0.98; 95% CI, 0.96-0.99; = 0.015; diabetic eye disease: OR, 0.92; 95% CI, 0.87-0.97; = 0.003) in the UKBB cohort. A paradoxical positive association was observed between AD and both glaucoma (OR, 1.30; 95% CI, 1.08-1.54; < 0.01) and cataract (OR, 1.15; 1.04-1.28; = 0.018). No association between the E4 allele and glaucoma was observed in either replication cohort (CLSA: OR, 1.03; 95% CI, 0.89-1.19; = 0.66; ANZRAG/BMES: OR, 0.97; 95% CI, 0.84-1.12; = 0.65).
A small negative association observed between E4 and glaucoma within the UKBB was not evident in either replication cohort and may represent an artifact of glaucoma underdiagnosis in E4 carriers.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
阐明载脂蛋白E（ApoE）E4等位基因与大型队列中青光眼患病率之间的潜在关联。
对基线数据和前瞻性收集的队列数据进行横断面分析。
英国生物银行（UKBB）中基因确定为欧洲血统的参与者（n = 438711）。使用从加拿大衰老纵向研究（CLSA；n = 18199）、澳大利亚和新西兰晚期青光眼登记处（ANZRAG；n = 1970）以及蓝山眼研究（BMES；n = 2440）招募的欧洲参与者收集的临床和基因分型数据进行重复分析。
确定载脂蛋白E等位基因和基因型，并根据青光眼状态比较其分布。使用与E4等位基因相关的阳性对照结局（死亡、痴呆、年龄相关性黄斑变性）和与E4等位基因无关的阴性对照结局（白内障、糖尿病眼病）进行类似分析。结局表型也与阿尔茨海默病（AD）相关，AD是一种与E4等位基因高度相关的临床结局。
E4基因型与表型比较的结果以比值比（OR）及其95%置信区间（CI）表示。重复分析在2个重复队列（CLSA和ANZRAG/BMES）中研究E4的关联。
在UKBB队列中，E4等位基因与青光眼呈负相关（OR，0.96；95%CI，0.93 - 0.99；P = 0.016），与两个阴性对照结局也呈负相关（白内障：OR，0.98；95%CI，0.96 - 0.99；P = 0.015；糖尿病眼病：OR，0.92；95%CI，0.87 - 0.97；P = 0.003）。在AD与青光眼（OR，1.30；95%CI，1.08 - 1.54；P < 0.01）和白内障（OR，1.15；1.04 - 1.28；P = 0.018）之间观察到矛盾的正相关。在两个重复队列中均未观察到E4等位基因与青光眼之间的关联（CLSA：OR，1.03；95%CI，0.89 - 1.19；P = 0.66；ANZRAG/BMES：OR，0.97；95%CI，0.84 - 1.12；P = 0.65）。
在UKBB中观察到的E4与青光眼之间的小的负相关在两个重复队列中均不明显，可能代表E4携带者中青光眼诊断不足的假象。
作者对本文讨论的任何材料均无所有权或商业利益。
