Relationship between single nucleotide polymorphisms in the 3′UTR of amyloid precursor protein and risk of Alzheimer’s disease and its mechanism

Abstract

<b>Background and objective:</b> Deregulation of the expression of amyloid precursor protein (APP) can lead to the development of Alzheimer's disease (AD). Recent studies have shown that many single nucleotide polymorphisms (SNPs) in the 3' untranslated region (UTR) of APP are associated with the development of AD. Since microRNAs (miRNAs) are involved in the regulation of APP expression, we believe that the APP 3'UTR polymorphism may affect the regulation of APP expression in miRNAs. <b>Results</b>: The levels of miR-101-3p, miR-153-3p, miR-144-3p, miR-381-3p, and miR-383-5p in plasma of patients with AD were significantly lower than those in the control group. The <i>APP</i>-534G/A site A allele was a protective factor for AD risk (adjusted odds ratio (OR) = 0.700, 95% confidence interval (95% CI): 0.573-0.840, <i>P</i><0.001). The <i>APP</i>-369C/G site variation was not associated with AD risk. The <i>APP</i>-118C/A site A allele was a protective factor for AD (adjusted OR = 0.762, 95% CI: 0.639-0.897, <i>P</i>=0.001). The <i>APP</i>-534G/A site mutation affects the regulation of APP protein expression by miR-101-3p, miR-144-3p, miR-153-3p, and miR-381-3p, and the mutation of the <i>APP</i>-118C/A site affects miR-101-3p, miR-144-3p, miR-153-3p, and miR-383-5p regulation of APP expression. <b>Conclusion:</b> APP 3'UTR polymorphisms can affect the regulation of APP expression by miRNAs and thus affect the occurrence of AD.