NOTCH4单核苷酸多态性与中国汉族人群脑动静脉畸形相关。
NOTCH4 Single-Nucleotide Polymorphism Is Associated with Brain Arteriovenous Malformation in a Chinese Han Population.
作者信息
Zhong Ming, Zhang Jianbo, Li Zhenjun, Liu Ziying, Fan Haiyan, Su Hengxian, Meng Hongliang, Zhang Xin, Li Xifeng, Duan Chuan-Zhi, He Xuying
机构信息
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,
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.
出版信息
Eur Neurol. 2023;86(2):107-115. doi: 10.1159/000526434. Epub 2023 Feb 1.
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.
引言
脑动静脉畸形（BAVMs）是一种高流量颅内血管畸形，其特征是动脉直接与静脉相连，中间没有毛细血管床。尽管发病率较低，但它们是颅内出血和癫痫的主要原因之一。血管生成、遗传、炎症和动静脉畸形综合征在BAVM形成中起重要作用。动物实验和先前的研究已证实NOTCH4可能与BAVM的发展有关。我们的研究确定了中国汉族人群中NOTCH4基因多态性与BAVM之间的联系。
方法
2017年6月至2019年7月，我们在南方医科大学珠江医院神经外科招募了150例经数字减影血管造影（DSA）确诊的BAVM患者。同时，150例无脑血管疾病的患者经计算机断层血管造影/磁共振血管造影/DSA确诊。从外周血中提取DNA，并通过PCR-连接酶检测反应鉴定NOTCH4基因型。采用χ2检验或Fisher精确检验评估BAVM组、对照组、出血组和其他并发症组之间等位基因和基因型频率的差异。
结果
两个单核苷酸多态性（SNP），rs443198和rs438475，与BAVM显著相关。没有SNP基因型与出血或癫痫显著相关。SNP rs443198_AA-SNP和rs438475_AA-SNP可能与较低的BAVM风险相关（p = 0.011，比值比（OR）=
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