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Research Paper|Volume 13, Issue 10|pp 13954—13967

S100B gene polymorphisms are associated with the S100B level and Alzheimer’s disease risk by altering the miRNA binding capacity

Jiafeng Wang1, Yulan Zhou2, Yixia Yang2, Xiang Gao1, Zhibin Liu1, Guanhao Hong1, Lifen Yao3, Jingwen Yin4, Xuefeng Gu5, Keshen Li6,7,8
  • 1Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
  • 2Clinical Medicine Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
  • 3Department of Neurology, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China
  • 4Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
  • 5Shanghai Key Laboratory of Molecular Imaging, Collaborative Research Center, Shanghai University of Medicine & Health Sciences, Shanghai, China
  • 6Department of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University, Guangzhou, China
  • 7Clinical Neuroscience Institute of Jinan University, Guangzhou, China
  • 8Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
* Equal contribution
Received: June 30, 2020Accepted: March 26, 2021Published: May 12, 2021
https://doi.org/10.18632/aging.203005

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

To examine the role of S100B in genetic susceptibility to Alzheimer’s disease (AD), we conducted a case-control study to analyze four polymorphism loci (rs2839364, rs1051169, rs2300403, and rs9722) of the S100B gene and AD risk. We found an independent increased risk of AD in ApoE ε4(-) subjects carrying the rs9722 AA-genotype (OR = 2.622, 95% CI = 1.399–4.915, P = 0.003). Further investigation revealed the serum S100B levels to be lower in rs9722 GG carriers than in rs9722 AA carriers (P = 0.003). We identified three miRNAs (miR-340-3p, miR-593-3p, miR-6827-3p) in which the seed match region covered locus rs9722. Luciferase assays indicated that the rs9722 G allele has a higher binding affinity to miR-6827-3p than the rs9722 A allele, leading to a significantly decreased fluorescence intensity. Subsequent western blot analysis showed that the S100B protein level of SH-SY5Y cells, which carry the rs9722 G allele, decreased significantly following miR-6827-3p stimulation (P = 0.009). The present study suggests that the rs9722 polymorphism may upregulate the expression of S100B by altering the miRNA binding capacity and may thus increase the AD risk. This finding would be of great help for the early diagnosis of AD.