DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent manner
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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1079455/full |
| _version_ | 1797957607359512576 |
|---|---|
| author | Tianqi Xu Tianqi Xu Xi Yu Shenjun Zhou Shenjun Zhou Yiwen Wu Xinpeng Deng Yuefei Wu Shiyi Wang Shiyi Wang Xiang Gao Sheng Nie Chenhui Zhou Chenhui Zhou Jie Sun Yi Huang Yi Huang |
| author_facet | Tianqi Xu Tianqi Xu Xi Yu Shenjun Zhou Shenjun Zhou Yiwen Wu Xinpeng Deng Yuefei Wu Shiyi Wang Shiyi Wang Xiang Gao Sheng Nie Chenhui Zhou Chenhui Zhou Jie Sun Yi Huang Yi Huang |
| author_sort | Tianqi Xu |
| collection | DOAJ |
| description | 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, p < .001). DNA hypomethylation can increase GSTA4 mRNA expression in human primary artery smooth muscle cells. The receiver operating characteristic (ROC) curve showed that GSTA4 mean methylation (AUC = .80, p < .001) was a reliable predictor of women intracranial aneurysm, among which CpG 1 exhibited the best predictive value (AUC = .89, p < .001). In addition, GSTA4 expression levels could also predict the risk of IA in women (AUC = .87, p = .005).Conclusion: Decreased DNA methylation and increased mRNA expression of the GSTA4 gene are associated with the risk of IA in women. |
| first_indexed | 2024-04-11T00:07:43Z |
| format | Article |
| id | doaj.art-78d850abe35c41888905d3c48aa30284 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T00:07:43Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-78d850abe35c41888905d3c48aa302842023-01-09T10:23:01ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-01-011310.3389/fgene.2022.10794551079455DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent mannerTianqi Xu0Tianqi Xu1Xi Yu2Shenjun Zhou3Shenjun Zhou4Yiwen Wu5Xinpeng Deng6Yuefei Wu7Shiyi Wang8Shiyi Wang9Xiang Gao10Sheng Nie11Chenhui Zhou12Chenhui Zhou13Jie Sun14Yi Huang15Yi Huang16Department of Neurology, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaDepartment of Neurology, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaDepartment of Neurology, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaMedical School of Ningbo University, Ningbo, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, Zhejiang, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo University, Ningbo, Zhejiang, ChinaObjective: 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, p < .001). DNA hypomethylation can increase GSTA4 mRNA expression in human primary artery smooth muscle cells. The receiver operating characteristic (ROC) curve showed that GSTA4 mean methylation (AUC = .80, p < .001) was a reliable predictor of women intracranial aneurysm, among which CpG 1 exhibited the best predictive value (AUC = .89, p < .001). In addition, GSTA4 expression levels could also predict the risk of IA in women (AUC = .87, p = .005).Conclusion: Decreased DNA methylation and increased mRNA expression of the GSTA4 gene are associated with the risk of IA in women.https://www.frontiersin.org/articles/10.3389/fgene.2022.1079455/fullintracranial aneurysmDNA methylationmRNA expression5-aza-2'-deoxycytidineglutathione S-tranferase alpha 4 |
| spellingShingle | Tianqi Xu Tianqi Xu Xi Yu Shenjun Zhou Shenjun Zhou Yiwen Wu Xinpeng Deng Yuefei Wu Shiyi Wang Shiyi Wang Xiang Gao Sheng Nie Chenhui Zhou Chenhui Zhou Jie Sun Yi Huang Yi Huang DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent manner Frontiers in Genetics intracranial aneurysm DNA methylation mRNA expression 5-aza-2'-deoxycytidine glutathione S-tranferase alpha 4 |
| title | DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent manner |
| title_full | DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent manner |
| title_fullStr | DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent manner |
| title_full_unstemmed | DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent manner |
| title_short | DNA methylation and mRNA expression of glutathione S-transferase alpha 4 are associated with intracranial aneurysms in a gender-dependent manner |
| title_sort | dna methylation and mrna expression of glutathione s transferase alpha 4 are associated with intracranial aneurysms in a gender dependent manner |
| topic | intracranial aneurysm DNA methylation mRNA expression 5-aza-2'-deoxycytidine glutathione S-tranferase alpha 4 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1079455/full |
| work_keys_str_mv | AT tianqixu dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT tianqixu dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT xiyu dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT shenjunzhou dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT shenjunzhou dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT yiwenwu dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT xinpengdeng dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT yuefeiwu dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT shiyiwang dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT shiyiwang dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT xianggao dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT shengnie dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT chenhuizhou dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT chenhuizhou dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT jiesun dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT yihuang dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner AT yihuang dnamethylationandmrnaexpressionofglutathionestransferasealpha4areassociatedwithintracranialaneurysmsinagenderdependentmanner |