Abstract
The purpose of this study was to evaluate the contribution of DNA methylation at the phospholipase A2 group VII (PLA2G7) gene, to the risk of developing brain arteriovenous malformations (BAVMs) and intracranial aneurysms (IAs) in a Han Chinese population. Seventy patients with BAVMs or IAs and 26 control subjects were recruited to evaluate PLA2G7 methylation by bisulfite pyrosequencing. CpG3 methylation at the PLA2G7 was significantly higher in BAVM patients than in the control group (Chr6,46735560, p = 0.042). Gender subgroup analysis showed that PLA2G7 CpG4 (Chr6,46735574, p = 0.033) and mean methylation (p = 0.037) levels were significantly associated with BAVM in males. However, in females, PLA2G7 methylations were much lower in IAs than in controls [CpG2 (Chr6,46735558), p = 0.030] and BAVMs [CpG2, p = 0.001; CpG4, p = 0.007; CpG6 (Chr6, 46735579), p = 0.024; mean, p = 0.013]. In addition, mean methylation of the PLA2G7 significantly correlated with apoB levels in all individuals (r = 0.288, p = 0.006), and with apoE in BAVM patients (r = 0.259, p = 0.016). The receiver operating characteristic (ROC) curve showed that PLA2G7 CpG3 methylation might be a predictor of BAVM risk in Han Chinese (area under curve (AUC) = 0.76, p = 0.008). PLA2G7 DNA methylation was significantly associated with the risk of developing BAVMs in males or IAs in females. Future studies on the PLA2G7 mechanisms should be performed on the pathogenesis of these cerebrovascular disorders.
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Funding
This study was supported by grants from the Zhejiang Provincial Natural Science Foundation of China (LQ17H090002), Medicine and Health Science and Technology projects of Zhejiang province (2018KY665, 2017KY610), and Ningbo Health Branding Subject Fund (PPXK2018-04).
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Y.H., J.S. and Z.L. contributed conception and design of the study; X.W., S.N., S.Z. and X.G. organized the patients and performed the experiments; Y.L. and S.X. performed the statistical analysis; Y.L. wrote the first draft of the manuscript; Y.H., X.W. and Y.L. wrote sections of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.
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Strengths and Limitations of This Study
1. PLA2G7 methylation significantly associated with the risk of BAVMs in Han Chinese males.
2. PLA2G7 methylation was correlated with the risk of IAs in Han Chinese females.
3. PLA2G7 methylation was significantly lower in IAs than BAVMs in Han Chinese females.
4. PLA2G7 methylation significantly correlated with apoB and apoE levels in Han Chinese.
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Liu, Y., Wu, X., Nie, S. et al. Methylation of Phospholipase A2 Group VII Gene Is Associated with Brain Arteriovenous Malformations in Han Chinese Populations. J Mol Neurosci 70, 1056–1063 (2020). https://doi.org/10.1007/s12031-020-01508-9
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DOI: https://doi.org/10.1007/s12031-020-01508-9