阿尔茨海默病中BIN1、CLU和APOE基因的联合风险效应。
The combined risk effect among BIN1, CLU, and APOE genes in Alzheimer's disease.
作者信息
Santos Lígia Ramos Dos, Almeida Jucimara Ferreira Figueiredo, Pimassoni Lúcia Helena Sagrillo, Morelato Renato Lírio, Paula Flavia de
机构信息
Universidade Federal do Espírito Santo, Centro de Ciências Humanas e Naturais, Departamento de Ciências Biológicas, Núcleo de Genética Humana e Molecular, Vitória, ES, Brazil.
Universidade Federal do Espírito Santo, Programa de Pós-Graduação em Biotecnologia, Vitória, ES, Brazil.
出版信息
Genet Mol Biol. 2020 Mar 16;43(1):e20180320. doi: 10.1590/1678-4685-GMB-2018-0320. eCollection 2020.
Genome-wide associations studies (GWAS) are detecting new variants associated with late-onset of Alzheimer's disease (LOAD), a multifactorial neurodegenerative disorder. The variants rs744373 BIN1, rs11136000 CLU and rs3764650 ABCA7 uncovered by GWAS led to different AD pathways, such as metabolism, trafficking and endocytosis of lipids and inflammation. However, most of the association studies did not replicate these variants with significance. This could be due to a small power effect evident when these variants are tested independently with LOAD. Therefore, we aimed to investigate whether the combination of different variants would additively modify the risk of association with LOAD that is observed in GWAS. We performed an association study testing pairwise variants in metabolism, trafficking and endocytosis of lipid (rs429358 and rs7412 APOE, rs744373 BIN1, rs3764650 ABCA7 and rs11136000 CLU) pathways with LOAD in samples from southeastern Brazil. Our data suggest a risk effect for LOAD between APOE with CLU and APOE with BIN1 genes.
全基因组关联研究（GWAS）正在检测与晚发性阿尔茨海默病（LOAD，一种多因素神经退行性疾病）相关的新变异。GWAS发现的rs744373（BIN1）、rs11136000（CLU）和rs3764650（ABCA7）变异导致了不同的AD途径，如脂质的代谢、运输和内吞作用以及炎症。然而，大多数关联研究并未显著重复这些变异。这可能是因为当这些变异与LOAD独立测试时，存在明显的小效应量。因此，我们旨在研究不同变异的组合是否会累加性地改变GWAS中观察到的与LOAD关联的风险。我们在巴西东南部的样本中进行了一项关联研究，测试脂质代谢、运输和内吞作用（rs429358和rs7412，APOE；rs744373，BIN1；rs3764650，ABCA7；rs11136000，CLU）途径中的成对变异与LOAD的关系。我们的数据表明，APOE与CLU基因以及APOE与BIN1基因之间存在LOAD风险效应。
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