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Research Paper|Volume 11, Issue 14|pp 5173—5191

Genetic polymorphisms and transcription profiles associated with intracranial aneurysm: a key role for NOTCH3

Mengqi Li1,2,5, Xinlong Dong1,2, Shi Chen1,2,4, Weihan Wang1,2, Chao Yang1,2, Bochuan Li6, Degang Liang5, Weidong Yang1,2, Xiaozhi Liu3, Xinyu Yang1,2
  • 1Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China
  • 2Tianjin Neurological Institute, Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin 300052, China
  • 3Department of Neurosurgery, Tianjin Fifth Central Hospital, Tianjin 300450, China
  • 4Department of Neurosurgery, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou 350007, China
  • 5Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
  • 6Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300052, China
* Equal contribution.
Received: April 7, 2019Accepted: July 16, 2019Published: July 23, 2019
https://doi.org/10.18632/aging.102111

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Intracranial aneurysm (IA) incidence is about 1~2%. However, the specific mechanisms of IA onset and development need further study. Our objective was to discover novel IA-related genes to determine possible etiologies further. We performed next-generation sequencing on nineteen Chinese patients with familial IA and one patient with sporadic IA. We obtained mRNA expression data of 129 samples from Gene Expression Omnibus (GEO) and made statistical computing to discover differentially expressed genes (DEGs). The screened IA-related gene NOTCH3 was determined by bioinformatic data mining. We verified the IA-related indicators of NOTCH3. Association was found between IA and the NOTCH3 SNPs rs779314594, rs200504060 and rs2285981. Levels of NOTCH3 mRNA were lower in IA tissue than in control tissue, but higher in peripheral blood neutrophils from IA patients than in neutrophils from controls. Levels of NOTCH3 protein were lower in IA tissue than in cerebral artery tissue. NOTCH3 also decreased the expression of angiogenesis factors in human umbilical vein endothelial cells. Variation in NOTCH3 and alteration of its expression in cerebral artery or neutrophils may contribute to IA. Our findings also describe a bioinformatic-experimental approach that may prove useful for probing the pathophysiology of other complex diseases.