title: Sex-dichotomous effects of NOS1AP promoter DNA methylation on intracranial aneurysm and brain arteriovenous malformation.
abstract: The goal of this study was to investigate the contribution of NOS1AP-promoter DNA methylation to the risk of intracranial aneurysm (IA) and brain arteriovenous malformation (BAVM) in a Han Chinese population. A total of 48 patients with IAs, 22 patients with BAVMs, and 26 control individuals were enrolled in the study. DNA methylation was tested using bisulfite pyrosequencing technology. We detected significantly higher DNA methylation levels in BAVM patients than in IA patients based on the multiple testing correction (CpG4-5 methylation: 5.86±1.04% vs. 4.37±2.64%, P=0.006). In women, CpG4-5 methylation levels were much lower in IA patients (3.64±1.97%) than in BAVM patients (6.11±1.20%, P<0.0001). However, in men, CpG1-3 methylation levels were much higher in the controls (6.92±0.78%) than in BAVM patients (5.99±0.70%, P=0.008). Additionally, there was a gender-based difference in CpG1 methylation within the controls (men vs. women: 5.75±0.50% vs. 4.99±0.53%, P=0.003) and BAVM patients (men vs. women: 4.70±0.74% vs. 5.50±0.87%, P=0.026). A subgroup analysis revealed significantly higher CpG3 methylation in patients who smoked than in those who did not (P=0.041). Our results suggested that gender modulated the interaction between NOS1AP promoter DNA methylation in IA and BAVM patients. Our results also confirmed that regular tobacco smoking was associated with increased NOS1AP methylation in humans. Additional studies with larger sample sizes are required to replicate and extend these findings.
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Zhepei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Jikuang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Keqing
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China.
authors.forename: Tiefeng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Zhejiang provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Pediatric Rheumatoid Immunology, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Yazhen
authors.initials: Y
authors.lastname: Di
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China. Electronic address: huangy102@gmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China. Electronic address: qinyuecui@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C488081:NOS1AP protein, human
keywords: Brain arteriovenous malformation; DNA methylation; Intracranial aneurysm; NOS1AP