DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent manner

作者：Tianqi Xu, Xi Yu, Shenjun Zhou, Yiwen Wu, Xinpeng Deng, Yuefei Wu, Shi‐Yi Wang, Xiang Gao, Sheng Nie, Chenhui Zhou, Jie Sun, Yi Huang · 发表于：Frontiers in Genetics · 年份：2023 · DOI：10.3389/fgene.2022.1079455 · 被引用次数：21 · 研究领域：Epigenetics and DNA Methylation、Moyamoya disease diagnosis and treatment、Neurological Complications and Syndromes

Objective: We performed a case-control study to investigate the correlation between DNA methylation and mRNA expression of the glutathione S-transferase alpha 4 ( GSTA4 ) gene and the risk of intracranial aneurysm (IA) in the Chinese Han population. Methods: After propensity score matching, 44 pairs of cases and controls were collected in this study. Fasting blood samples were collected for DNA and RNA extraction within 24 h of admission. Nine CpG dinucleotides were selected from the GSTA4 promoter region for DNA methylation pyrosequencing. mRNA expression of GSTA4 was measured by quantitative real-time polymerase chain reaction (RT-qPCR). In vitro cell experiments were conducted to verify the association between 5-aza-2′-deoxycytidine induced DNA hypomethylation and GSTA4 mRNA expression. Results: The mean methylation level of GSTA4 was much lower in IA patients, especially in IA patients, especially in unruptured IA (UIA), than that in controls (IA vs. Control, p < .001; ruptured IA (RIA) vs. Control, p = .005; UIA vs. Control, p < .001). With sex stratification, we further found that the association between GSTA4 methylation and IA risk presented only in women (mean methylation level: IA vs. Control, p < .001; RIA vs. Control, p = .009; UIA vs. Control, p < .001). GSTA4 mRNA expression was significantly higher in the IA group than in the control group ( p < .01) and negatively correlated with DNA methylation in all individuals (r = −.746,...