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. 2024 Mar 29;44(3):BSR20231374.
doi: 10.1042/BSR20231374.

Exploring the potential of VGLL3 methylation as a prognostic indicator for intracranial aneurysm with gender-specific considerations

Yuchun Liu  1   2 , Siqi Chen  1   2   3 , Enhao Zhang  1   2   3 , Yinbin Xu  1   2   3 , Xinpeng Deng  1   2   3 , Ziliang Hu  1   2   3 , Sheng Nie  1   2 , Yinglu Lin  4 , Yi Huang  1   2   3
Affiliations

Exploring the potential of VGLL3 methylation as a prognostic indicator for intracranial aneurysm with gender-specific considerations

Yuchun Liu et al. Biosci Rep. .

Abstract

DNA methylation is widely recognized to play a role in intracranial aneurysm (IA) pathogenesis. We investigated the levels of methylation of vestigial-like 3 (VGLL3) in IA and explored its potential as a prognostic indicator. A total of 48 patients with IA and 48 healthy controls were included in the present study. Methylation levels of CpG sites were assessed using bisulfite pyrosequencing, and levels of VGLL3, TEAD, and YAP in the blood were measured by real-time quantitative polymerase chain reaction testing. VGLL3 methylation was significantly higher in controls than in IA patients (P=0.001), and this phenomenon was more pronounced in females (P<0.001). Compared with the control group, the expression levels of VGLL3 and TEAD in the blood of IA patients were significantly increased, while YAP was significantly decreased. VGLL3 methylation was positively correlated with HDL (P=0.003) and female Lpa concentration (r = 0.426, P=0.03), and was also negatively correlated with age (P=0.003), APOE (P=0.005), and VGLL3 mRNA expression (P<0.001). Methylation and mRNA expression of VGLL3 may serve as indicators of IA risk in females (AUC = 0.810 and 0.809). VGLL3 methylation may participate in the pathogenesis of IA by regulating the expression of the VGLL3/TEAD/YAP pathway, and its gene methylation and expression levels have IA risk prediction value.

Keywords: CpG island; DNA Methylation; intracranial aneurysm; vestigial-like 3.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1. The locations and analysis of the twelve CpGs in VGLL3 gene
(A) The locations of the 12 CpGs in VGLL3 gene. (B) Representative sequencing analysis of 12 methylation sites.
Figure 2
Figure 2. Correlation analysis between VGLL3 methylation degree and various clinical features
(A) Correlation analysis in all groups. (B) Correlation analysis in all males. (C) Correlation analysis in all females. (D) Correlation of VGLL3 methylation with HDL in all sex. (E) Correlation of VGLL3 methylation with ApoE in all sex. (F) Correlation of VGLL3 methylation with HDL in males. (G) Correlation of VGLL3 methylation with age in males. (H) Correlation of VGLL3 methylation with HDL in females. (I) Correlation of VGLL3 methylation with Lp (a) in females. (J) Correlation of VGLL3 methylation with ApoE in females. Pearson correlation analysis was employed for data analysis.
Figure 3
Figure 3. The significant association between VGLL3 mRNA expression and DNA methylation
(A) VGLL3 mRNA expression was much higher in IA than in healthy control. (B) VGLL3 mRNA expression was much higher in UIA patients. (C) Correlation between VGLL3 expression and methylation of each CpG site. (D) The VGLL3 expression was significantly associated with mean DNA methylation in all individuals. (E) TEAD expression was much higher in IA than in healthy control. (F) YAP expression was much higher in IA than in healthy control. RIA: ruptured intracranial aneurysm; UIA: unruptured intracranial aneurysm; *P<0.05.
Figure 4
Figure 4. ROC cure of VGLL3 gene DNA methylation in IA patients
(A,B) ROC curve for VGLL3 DNA methylation in all sexes. (C,D) ROC curve for VGLL3 DNA methylation in male. (E,F) ROC curve for VGLL3 DNA methylation in females; (G) ROC curve for VGLL3 mRNA expression.
Figure 5
Figure 5. VGLL3 methylation may participate in the pathogenesis of IA by regulating the expression of the VGLL3/TEAD/YAP pathway
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