Neurosciences Research Group, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia.
Alzheimer Dis Assoc Disord. 2022;36(1):29-35. doi: 10.1097/WAD.0000000000000477.
The Apolipoprotein E (APOE) gene is the main risk factor for late-onset Alzheimer disease (LOAD). Genetic variants and haplotypes in regions near the APOE locus may be associated with LOAD in the Colombian population.
We evaluated frequencies and risk of genetic variants and haplotypes in APOE, TOMM40, and APOC1 promoters, also in putative regulatory enhancer elements (TOMM40 IVS2-4 and TOMM40 IVS6), and in cis-regulatory elements (ME1 and BCR).
Our case-control association study was carried out in 50 patients with LOAD and 50 controls. We determined frequencies and odd ratios for genetic variants and haplotypes.
We found a significant association between LOAD and genetic variants at the TOMM40 promoter, at TOMM40 IVS2-4 and TOMM40 IVS6 regulatory enhancer elements, and at the APOC1 promoter. Particularly, variants of Poly-T and APOC1 promoter could anticipate the age of onset of LOAD in our population. We identified three risk haplotypes in TOMM40 (ACGGAG, ACGGGG, and ATAGGC) related to LOAD's age of onset. We also found other risk or protection haplotypes at the TOMM40 and APOE promoters, at TOMM40 IVS2-4, TOMM40 IVS6 regulatory enhancer elements, and at ME1.
Genetic variants and haplotypes near the APOE locus are related to LOAD risk and accelerated onset of LOAD in the Colombian population.
载脂蛋白 E（APOE）基因是晚发性阿尔茨海默病（LOAD）的主要风险因素。APOE 基因座附近区域的遗传变异和单倍型可能与哥伦比亚人群中的 LOAD 相关。
我们评估了 APOE、TOMM40 和 APOC1 启动子中的遗传变异和单倍型、TOMM40 IVS2-4 和 TOMM40 IVS6 潜在调控增强子元件以及顺式调控元件（ME1 和 BCR）的频率和风险。
我们的病例对照关联研究在 50 名 LOAD 患者和 50 名对照中进行。我们确定了遗传变异和单倍型的频率和比值比。
我们发现 TOMM40 启动子、TOMM40 IVS2-4 和 TOMM40 IVS6 调控增强子元件以及 APOC1 启动子的遗传变异与 LOAD 之间存在显著关联。特别是，TOMM40 启动子中的 Poly-T 和 APOC1 变体可以预测我们人群中 LOAD 的发病年龄。我们在 TOMM40 中鉴定了三个与 LOAD 发病年龄相关的风险单倍型（ACGGAG、ACGGGG 和 ATAGGC）。我们还在 TOMM40 和 APOE 启动子、TOMM40 IVS2-4、TOMM40 IVS6 调控增强子元件以及 ME1 中发现了其他风险或保护单倍型。
APOE 基因座附近的遗传变异和单倍型与 LOAD 风险以及哥伦比亚人群中 LOAD 的发病年龄加速有关。
