School of Pharmacy and Medical Sciences, University of South Australia, Adelaide.
CSIRO Health and Biosecurity, Adelaide, Australia.
J Gerontol A Biol Sci Med Sci. 2020 Sep 25;75(10):1899-1905. doi: 10.1093/gerona/glz259.
APOE ε4 allele is an established risk factor for Alzheimer's disease and hypercholesterolemia. However, its association with metabolic and genetic risk factors related to glycation is not clear. We tested the hypothesis that, apart from high plasma cholesterol, APOE ε4 carriers may also have higher advanced glycation end products (AGEs) and total soluble extracellular domain of RAGE (sRAGE) and that these biomarkers may be modified by the common Gly82Ser (G82S) polymorphism (rs2070600) in the RAGE gene. To test this, we measured these biomarkers in 172 healthy cognitively normal individuals, of which 32 were APOE ε4 carriers and 140 noncarriers. APOE ε4 carriers showed higher levels of cholesterol (p < .001), glyoxal (p < .001), fluorescent AGEs (p < .001), Nε-carboxymethyllysine (p < .001) and sRAGE (p = .018) when compared to noncarriers. Furthermore, sRAGE was also higher in those that did not carry the A allele of the RAGE gene that codes for serine instead of glycine (p = .034). Our study indicates that APOE ε4 carriers have a greater propensity to glycation than noncarriers which may further increase their risk for diabetes and dementia. The increased sRAGE levels in APOE ε4 carriers suggests a defensive response against AGEs that may be further influenced by the RAGE G82S polymorphism.
载脂蛋白 E ε4 等位基因是阿尔茨海默病和高胆固醇血症的既定风险因素。然而，其与糖化相关的代谢和遗传风险因素的关联尚不清楚。我们检验了这样一个假设，即除了高血浆胆固醇外，载脂蛋白 E ε4 携带者可能还具有更高的晚期糖基化终产物 (AGEs) 和总可溶性细胞外结构域 RAGE (sRAGE)，并且这些生物标志物可能会受到 RAGE 基因中常见的 Gly82Ser (G82S) 多态性 (rs2070600) 的影响。为了验证这一点，我们在 172 名健康认知正常的个体中测量了这些生物标志物，其中 32 名是载脂蛋白 E ε4 携带者，140 名是非携带者。与非携带者相比，载脂蛋白 E ε4 携带者的胆固醇（p <.001）、乙二醛（p <.001）、荧光 AGEs（p <.001）、Nε-羧甲基赖氨酸（p <.001）和 sRAGE（p =.018）水平更高。此外，在不携带 RAGE 基因编码丝氨酸而不是甘氨酸的 A 等位基因的个体中，sRAGE 也更高（p =.034）。我们的研究表明，载脂蛋白 E ε4 携带者比非携带者更容易发生糖化，这可能会进一步增加他们患糖尿病和痴呆的风险。载脂蛋白 E ε4 携带者中 sRAGE 水平的升高表明，可能是对 AGEs 的防御反应，而这种反应可能会进一步受到 RAGE G82S 多态性的影响。
