Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain.
BioCruces Bizkaia Health Research Institute, Barakaldo, Spain.
Mol Neurobiol. 2021 Jan;58(1):55-64. doi: 10.1007/s12035-020-02103-0. Epub 2020 Sep 6.
Late-onset Alzheimer's disease (LOAD) is a neurodegenerative disorder of growing relevance in an aging society for which predictive biomarkers are needed. Many genes involved in LOAD are tightly controlled by microRNAs (miRNAs), which can be modulated by single-nucleotide polymorphisms (SNPs). Our aim was to determine the association between SNPs in miRNAs and LOAD. We selected all SNPs in pre-miRNAs with a minor allele frequency (MAF) > 1% and genotyped them in a cohort of 229 individuals diagnosed with LOAD and 237 unrelated healthy controls. In silico analyses were performed to predict the effect of SNPs on miRNA stability and detect downstream pathways. Four SNPs were associated with LOAD risk with a p value < 0.01 (rs74704964 in hsa-miR-518d, rs71363366 in hsa-miR-1283-2, rs11983381 in hsa-miR-4653, and rs10934682 in hsa-miR-544b). In silico analyses support a possible functional effect of those SNPs in miRNA levels and in the regulation of pathways of relevance for the development of LOAD. Although the results are promising, additional studies are needed to validate the association between SNPs in miRNAs and the risk of developing LOAD. Graphical abstract.
迟发性阿尔茨海默病（LOAD）是老龄化社会中越来越重要的神经退行性疾病，需要预测生物标志物。许多参与 LOAD 的基因受到 microRNAs（miRNAs）的紧密调控，miRNAs 可以通过单核苷酸多态性（SNPs）进行调节。我们的目的是确定 miRNA 中的 SNPs 与 LOAD 之间的关联。我们选择了所有 MAF > 1%的 pre-miRNA 中的 SNPs，并在 229 名确诊为 LOAD 的患者和 237 名无关的健康对照者的队列中对其进行了基因分型。进行了计算机分析以预测 SNPs 对 miRNA 稳定性的影响并检测下游途径。有四个 SNPs 与 LOAD 风险相关，p 值 < 0.01（hsa-miR-518d 中的 rs74704964、hsa-miR-1283-2 中的 rs71363366、hsa-miR-4653 中的 rs11983381 和 hsa-miR-544b 中的 rs10934682）。计算机分析支持这些 SNPs 在 miRNA 水平和与 LOAD 发生发展相关的途径调节中可能具有功能作用。尽管结果很有希望，但需要进一步的研究来验证 miRNA 中 SNPs 与 LOAD 发病风险之间的关联。图表摘要。
