NOTCH4 Single-Nucleotide Polymorphism Is Associated with Brain Arteriovenous Malformation in a Chinese Han Population

Clinical Neurology: Research Article

Zhong M. · Zhang J. · Li Z. · Liu Z. · Fan H. · Su H. · Meng H. · Zhang X. · Li X. · Duan C.-Z. · He X.

Author affiliations

The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China

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Article / Publication Details

First-Page Preview

Abstract of Clinical Neurology: Research Article

Received: May 26, 2022
Accepted: July 09, 2022
Published online: February 01, 2023

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 6

ISSN: 0014-3022 (Print)
eISSN: 1421-9913 (Online)

For additional information: https://www.karger.com/ENE

Abstract

Introduction: Brain arteriovenous malformations (BAVMs) are high-flow intracranial vascular malformations characterized by the direct connection of arteries to veins without an intervening capillary bed. They are one of the main causes of intracranial hemorrhage and epilepsy, although morbidity is low. Angiogenesis, heredity, inflammation, and arteriovenous malformation syndromes play important roles in BAVM formation. Animal experiments and previous studies have confirmed that NOTCH4 may be associated with BAVM development. Our study identifies a connection between NOTCH4 gene polymorphisms and BAVM in a Chinese Han population. Methods: We enrolled 150 patients with BAVMs confirmed by digital subtraction angiography (DSA) in the Department of Neurosurgery, Zhujiang Hospital, Southern Medical University from June 2017 to July 2019. Simultaneously, 150 patients without cerebrovascular disease were confirmed by computed tomography angiography/magnetic resonance angiography/DSA. DNA was extracted from peripheral blood and NOTCH4 genotypes were identified by PCR-ligase detection reaction. The χ2 test or Fisher’s exact test was used to evaluate the differences in allele and genotype frequencies between the BAVM group, control group, bleeding group, and other complications. Results: Two single-nucleotide polymorphisms (SNPs), rs443198 and rs438475, were significantly associated with BAVM. No SNP genotypes were significantly associated with hemorrhage or epilepsy. SNPs rs443198_AA-SNP and rs438475_AA-SNP may be associated with a lower risk of BAVM (p = 0.011, odds ratio (OR) = 0.459, 95% confidence interval (CI): 0.250–0.845; p = 0.033, OR = 0.759, 95% CI: 0.479–1.204). Conclusion: NOTCH4 gene polymorphisms were associated with BAVM and may be a risk factor in a Chinese Han population.

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References Barreau X, Marnat G, Gariel F, Dousset V. Intracranial arteriovenous malformations. Diagn Interv Imaging. 2014 Dec;95(12):1175–86. Fleetwood IG, Steinberg GK. Arteriovenous malformations. Lancet. 2002 Mar 9;359(9309):863–73. Hofmeister C, Stapf C, Hartmann A, Sciacca RR, Mansmann U, terBrugge K, et al. Demographic, morphological, and clinical characteristics of 1289 patients with brain arteriovenous malformation. Stroke. 2000 Jun;31(6):1307–10. Gabriel RA, Kim H, Sidney S, McCulloch CE, Singh V, Johnston SC, et al. Ten-year detection rate of brain arteriovenous malformations in a large, multiethnic, defined population. Stroke. 2010 Jan;41(1):21–6. Englot DJ, Young WL, Han SJ, McCulloch CE, Chang EF, Lawton MT, et al. Seizure predictors and control after microsurgical resection of supratentorial arteriovenous malformations in 440 patients. Neurosurgery. 2012 Sep;71(3):572–80; discussion 580. Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (Aruba): a multicentre, non-blinded, randomised trial. Lancet. 2014 Feb 15;383(9917):614–21. Lawton MT, Rutledge WC, Kim H, Stapf C, Whitehead KJ, Li DY, et al. Brain arteriovenous malformations. Nat Rev Dis Primers. 2015 May 28;1:15008. Weinsheimer SM, Xu H, Achrol AS, Stamova B, McCulloch CE, Pawlikowska L, et al. Gene expression profiling of blood in brain arteriovenous malformation patients. Transl Stroke Res. 2011;2(4):575–87. Weinsheimer S, Bendjilali N, Nelson J, Guo DE, Zaroff JG, Sidney S, et al. Genome-wide association study of sporadic brain arteriovenous malformations. J Neurol Neurosurg. 2016 Sep;87(9):916–23. Terzic T, Kastelic M, Dolzan V, Plesničar BK. Genetic variability testing of neurodevelopmental genes in schizophrenic patients. J Mol Neurosci. 2015 May;56(1):205–11. Sturiale CL, Puca A, Sebastiani P, Gatto I, Albanese A, Di Rocco C, et al. Single nucleotide polymorphisms associated with sporadic brain arteriovenous malformations: where do we stand? Brain. 2013 Feb;136(Pt 2):665–81. Hashimoto T, Lawton MT, Wen G, Yang GY, Chaly T Jr, Stewart CL, et al. Gene microarray analysis of human brain arteriovenous malformations. Neurosurgery. 2004 Feb;54(2):410–23; discussion 423-5. Kume T. Specification of arterial, venous, and lymphatic endothelial cells during embryonic development. Histol Histopathol. 2010 May;25(5):637–46. Lawson ND, Vogel AM, Weinstein BM. Sonic hedgehog and vascular endothelial growth factor act upstream of the NOTCH pathway during arterial endothelial differentiation. Dev Cell. 2002 Jul;3(1):127–36. Delev D, Pavlova A, Grote A, Boström A, Höllig A, Schramm J, et al. NOTCH4 gene polymorphisms as potential risk factors for brain arteriovenous malformation development and hemorrhagic presentation. J Neurosurgery. 2017 May;126(5):1552–9. Murphy PA, Lu G, Shiah S, Bollen AW, Wang RA. Endothelial NOTCH signaling is upregulated in human brain arteriovenous malformations and a mouse model of the disease. Lab Invest. 2009 Sep;89(9):971–82. Zhuge Q, Wu Z, Huang L, Zhao B, Zhong M, Zheng W, et al. NOTCH4 is activated in endothelial and smooth muscle cells in human brain arteriovenous malformations. J Cell Mol Med. 2013 Nov;17(11):1458–64. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005 Jan 15;21(2):263–5. Mouchtouris N, Jabbour PM, Starke RM, Hasan DM, Zanaty M, Theofanis T, et al. Biology of cerebral arteriovenous malformations with a focus on inflammation. J Cereb Blood Flow Metab. 2015 Feb;35(2):167–75. Shenkar R, Elliott JP, Diener K, et al. Differential gene expression in human cerebrovascular malformations. Neurosurgery. 2003;52(2):465–77. Article / Publication Details

First-Page Preview

Abstract of Clinical Neurology: Research Article

Received: May 26, 2022
Accepted: July 09, 2022
Published online: February 01, 2023

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 6

ISSN: 0014-3022 (Print)
eISSN: 1421-9913 (Online)

For additional information: https://www.karger.com/ENE

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