A Genome-Wide Study of Single-Nucleotide Polymorphisms in MicroRNAs and Further In Silico Analysis Reveals Their Putativ
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ORIGINAL ARTICLE
A Genome-Wide Study of Single-Nucleotide Polymorphisms in MicroRNAs and Further In Silico Analysis Reveals Their Putative Role in Susceptibility to Late-Onset Alzheimer’s Disease Soraya Herrera-Espejo 1 & Borja Santos-Zorrozua 1 & Paula Alvarez-Gonzalez 1 & Idoia Martin-Guerrero 1,2 & Marian M. de Pancorbo 3 & Africa Garcia-Orad 1,2 & Elixabet Lopez-Lopez 1,2 Received: 16 December 2019 / Accepted: 27 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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-miR544b). 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. Keywords Single nucleotide polymorphisms . MicroRNAs . Late-onset Alzheimer’s disease . Susceptibility
Introduction Alzheimer’s disease (AD) is an irreversible progressive neurodegenerative disease that affects the central nervous system Soraya Herrera-Espejo and Borja Santos-Zorrozua share the first authorship. Africa Garcia-Orad and Elixabet Lopez-Lopez share the last authorship. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02103-0) contains supplementary material, which is available to authorized users. * Elixabet Lopez-Lopez [email protected] 1
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
2
BioCruces Bizkaia Health Research Institute, Barakaldo, Spain
3
BIOMICs Research Group, Centro de Investigación “Lascaray” Ikergunea, University of the Basque Country (UPV/EHU), Leioa, Spain
and encompasses > 80% of dementia cases in people older than 65 [1], harming more than 25 million people around the world [2]. Since AD has a preclinical stage that starts 15 to 20 years prior to diagnosis [3] and postmortem studies have revealed that the brains of people without a diagnosis of cognitive impairment or with mild cognitive impairment often present similar histopathological hallmarks to AD patients [4
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