DNA methylation of the MAP3K10 gene may participate in the development of intracranial aneurysm

Abstract

Background: The goal of this study was to explore the association between mitogen-activated protein kinase kinase kinase 10 (MAP3K10) methylation and blood lipid levels and intracranial aneurysm (IA) risk.

Materials and methods: A total of 96 age- and sex-matched investigators participated in the assessment of MAP3K10 methylation. Fourteen CpG sites of the MAP3K10 gene were selected for methylated-pyrosequencing. Human brain vascular smooth muscle cell was used to assess the regulatory role of DNA methylation in MAP3K10 gene transcription.

Results: MAP3K10 mean methylation was positively correlated with triglyceride (TG, r = 0.388; p = 0.007) in men, but negatively correlated with TG (r = -0.434; p = 0.002) in women. MAP3K10 methylation in patients with IA was significantly lower than that in controls (p < 0.05), and this phenomenon was more significant in women (12 CpG sites presented significance at p < 0.05). MAP3K10 methylation might be a potential predictor of the risk of IA (CpG1, AUC = 0.81, p < 0.001; mean methylation, AUC = 0.69, p = 0.001). The predictive value was also more significant in women (CpG1: AUC = 0.86, p < 0.001; mean methylation: AUC = 0.73, p = 0.006). No significant association was found between DNA methylation and MAP3K10 gene transcription in vitro experiment.

Conclusion: Patients with IA had lower MAP3K10 methylation levels than healthy controls. MAP3K10 methylation may be a potential predictor of IA risk, particularly in women.

Keywords: Atherosclerosis; DNA methylation; Intracranial aneurysm; MAP3K10; Triglyceride.