The Apolipoprotein E (APOE) e4 allele is associated with reduced longevity and increased Coronary Artery Disease (CAD) and Alzheimer's disease, with e4e4 having markedly larger effect sizes than e3e4. The e2 longevity promoting variant is less studied. We conducted a phenome-wide association study of ApoE e2e3 and e2e2 with aging phenotypes, to assess their potential as targets for anti-aging interventions. Data were from 379,000 UK Biobank participants, aged 40 to 70 years. e2e3 (n=46,535) had mostly lower lipid-related biomarker levels including reduced total and LDL-cholesterol, and lower risks of CAD (Odds Ratio=0.87, 95% CI: 0.83 to 0.90, p=4.92×10^-14) and hypertension (OR=0.94, 95% CI: 0.92 to 0.97, p=7.28×10^-7) versus e3e3. However, lipid changes in e2e2 (n=2,398) were more extreme, including a marked increase in triglyceride levels (0.41 Standard Deviations, 95% CI: 0.37 to 0.45, p=5.42×10^-92), with no associated changes in CAD risks. There were no associations with biomarkers of kidney function. The effects of both e2e2 and e2e3 were minimal on falls, muscle mass, grip strength or frailty. In conclusion, e2e3 has protective effects on some health outcomes, but the effects of e2e2 are not similar, complicating the potential usefulness of e2 as a target for anti-aging intervention.

中文翻译：

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英国379,000名生物库参与者的ApoE e2和与衰老相关的结果

的载脂蛋白E（APOE）E4等位基因与降低长寿相关和增加的冠状动脉疾病（CAD）和阿尔茨海默氏病，与具有显着更大的效果尺寸小于E3E4 e4e4。e2长寿促进变体的研究较少。我们进行了ApoE e2e3和e2e2与衰老表型的全现象关联研究，以评估它们作为抗衰老干预目标的潜力。数据来自379,000位年龄在40至70岁之间的英国生物银行参与者。e2e3（n = 46,535）的脂质相关生物标志物水平较低，包括总胆固醇和LDL胆固醇降低，以及CAD风险较低（几率= 0.87，95％CI：0.83至0.90，p = 4.92×10 ^-14）和高血压（OR = 0.94，95％CI：0.92至0.97，p = 7.28×10 ^-7）与e3e3。然而，e2e2中的脂质变化（n = 2,398）更为极端，包括甘油三酸酯水平显着增加（0.41标准偏差，95％CI：0.37至0.45，p = 5.42×10 ^-92），而CAD没有相关变化风险。与肾脏功能的生物标志物没有关联。e2e2和e2e3对跌倒，肌肉质量，抓地力或身体虚弱的影响极小。总之，e2e3对某些健康结局具有保护作用，但e2e2的作用并不相似，这使e2作为抗衰老干预目标的潜在用途变得复杂。