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

Biosci Rep. 2019 May 2;39(5):BSR20182485. doi: 10.1042/BSR20182485. Print 2019 May 31.

Abstract

Background and objective: 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. Results: 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 APP-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, P<0.001). The APP-369C/G site variation was not associated with AD risk. The APP-118C/A site A allele was a protective factor for AD (adjusted OR = 0.762, 95% CI: 0.639-0.897, P=0.001). The APP-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 APP-118C/A site affects miR-101-3p, miR-144-3p, miR-153-3p, and miR-383-5p regulation of APP expression. Conclusion: APP 3'UTR polymorphisms can affect the regulation of APP expression by miRNAs and thus affect the occurrence of AD.

Keywords: Alzheimer’s disease; amyloid precursor protein; microRNA; single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / blood
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / blood
  • Amyloid beta-Protein Precursor / genetics*
  • Female
  • Gene Expression Regulation / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • HeLa Cells
  • Humans
  • Male
  • MicroRNAs / blood
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors

Substances

  • 3' Untranslated Regions
  • APP protein, human
  • Amyloid beta-Protein Precursor
  • MIRN101 microRNA, human
  • MIRN144 microRNA, human
  • MIRN153 microRNA, human
  • MIRN381 microRNA, human
  • MIRN383 microRNA, human
  • MicroRNAs