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

Background: Brain arteriovenous malformations (BAVMs) are high-flow intracranial vascular malformations characterized by the direct connection of arteries to veins without an intervening capillary bed. It is one of the main causes of intracranial hemorrhage and epilepsy though 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. Chi-square test or Fisher’s exact test was used to evaluate the difference in allele and genotype frequencies between the BAVM group, control group, bleeding, 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 and epilepsy. SNPs rs443198_ AA-SNP and rs438475_ AA-SNP may be associated with lower risk of BAVM (P = 0.011, OR = 0.459, 95% 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.