DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males
Objective: This study is aimed to investigate the contribution of patatin-like phospholipase domain-containing protein 6 (PNPLA6) DNA methylation to the risk of intracranial aneurysm (IA) in the Han Chinese population.Methods: A total of 96 age- and sex-matched participants were recruited to evaluat...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.885680/full |
| _version_ | 1811218940064432128 |
|---|---|
| author | Shengjun Zhou Shengjun Zhou Junjun Zhang Chenhui Zhou Chenhui Zhou Fanyong Gong Xueli Zhu Xingqiang Pan Jie Sun Xiang Gao Yi Huang Yi Huang Yi Huang |
| author_facet | Shengjun Zhou Shengjun Zhou Junjun Zhang Chenhui Zhou Chenhui Zhou Fanyong Gong Xueli Zhu Xingqiang Pan Jie Sun Xiang Gao Yi Huang Yi Huang Yi Huang |
| author_sort | Shengjun Zhou |
| collection | DOAJ |
| description | Objective: This study is aimed to investigate the contribution of patatin-like phospholipase domain-containing protein 6 (PNPLA6) DNA methylation to the risk of intracranial aneurysm (IA) in the Han Chinese population.Methods: A total of 96 age- and sex-matched participants were recruited to evaluate PNPLA6 methylation via bisulfite pyrosequencing. The PNPLA6 mRNA expression in the plasma was determined using real-time quantitative reverse transcription-polymerase chain reaction. Human primary artery smooth muscle cells (HPCASMC) were used for the in vitro function study.Results: PNPLA6 methylation was significantly higher in patients with IA than in healthy controls (p < 0.01). Sex group analysis showed that this correlation appeared in the male group (p < 0.01) but not in the female group (p > 0.05). PNPLA6 methylation was significantly associated with age in all participants (r = 0.306, p = 0.003) and in the control group (r = 0.377, p = 0.008) but not in the IA group (r = 0.127, p = 0.402). Furthermore, the PNPLA6 mRNA expression significantly decreased in patients with IA than that in the controls (p = 0.016). PNPLA6 expression was significantly inversely correlated with elevated DNA methylation in participants (r = −0.825, p < 0.0001). In addition, PNPLA6 transcription was significantly enhanced following treatment with 5-aza-2’-deoxycytidine methylation inhibitor in HPCASMC.The receiver operating characteristic analyses of curves showed that the PNPLA6 mean methylation [area under the curve (AUC) = 0.74, p < 0.001] and mRNA expression (AUC = 0.86, p < 0.001) could have a diagnostic value for patients with IA.Conclusion: Although future functional experiments are required to test our hypothesis, our study demonstrated that PNPLA6 methylation and mRNA expression were significantly associated with the risk of IA; thus, they show potential for use in the early diagnosis of IA. |
| first_indexed | 2024-04-12T07:17:36Z |
| format | Article |
| id | doaj.art-c65e153a359f436fa1e01d219fb2377b |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-12T07:17:36Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-c65e153a359f436fa1e01d219fb2377b2022-12-22T03:42:26ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-07-011410.3389/fnagi.2022.885680885680DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in MalesShengjun Zhou0Shengjun Zhou1Junjun Zhang2Chenhui Zhou3Chenhui Zhou4Fanyong Gong5Xueli Zhu6Xingqiang Pan7Jie Sun8Xiang Gao9Yi Huang10Yi Huang11Yi Huang12Department of Neurosurgery, Ningbo First Hospital, Ningbo, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo, ChinaDepartment of Ultrasound, Ningbo First Hospital, Ningbo, ChinaNingbo Center for Disease Control and Prevention, Ningbo, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo, ChinaDepartment of Neurosurgery, Ningbo First Hospital, Ningbo, ChinaKey Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, ChinaMedical Research Center, Ningbo First Hospital, Ningbo, ChinaObjective: This study is aimed to investigate the contribution of patatin-like phospholipase domain-containing protein 6 (PNPLA6) DNA methylation to the risk of intracranial aneurysm (IA) in the Han Chinese population.Methods: A total of 96 age- and sex-matched participants were recruited to evaluate PNPLA6 methylation via bisulfite pyrosequencing. The PNPLA6 mRNA expression in the plasma was determined using real-time quantitative reverse transcription-polymerase chain reaction. Human primary artery smooth muscle cells (HPCASMC) were used for the in vitro function study.Results: PNPLA6 methylation was significantly higher in patients with IA than in healthy controls (p < 0.01). Sex group analysis showed that this correlation appeared in the male group (p < 0.01) but not in the female group (p > 0.05). PNPLA6 methylation was significantly associated with age in all participants (r = 0.306, p = 0.003) and in the control group (r = 0.377, p = 0.008) but not in the IA group (r = 0.127, p = 0.402). Furthermore, the PNPLA6 mRNA expression significantly decreased in patients with IA than that in the controls (p = 0.016). PNPLA6 expression was significantly inversely correlated with elevated DNA methylation in participants (r = −0.825, p < 0.0001). In addition, PNPLA6 transcription was significantly enhanced following treatment with 5-aza-2’-deoxycytidine methylation inhibitor in HPCASMC.The receiver operating characteristic analyses of curves showed that the PNPLA6 mean methylation [area under the curve (AUC) = 0.74, p < 0.001] and mRNA expression (AUC = 0.86, p < 0.001) could have a diagnostic value for patients with IA.Conclusion: Although future functional experiments are required to test our hypothesis, our study demonstrated that PNPLA6 methylation and mRNA expression were significantly associated with the risk of IA; thus, they show potential for use in the early diagnosis of IA.https://www.frontiersin.org/articles/10.3389/fnagi.2022.885680/fullPNPLA6DNA methylationmRNA expressionageintracranial aneurysms |
| spellingShingle | Shengjun Zhou Shengjun Zhou Junjun Zhang Chenhui Zhou Chenhui Zhou Fanyong Gong Xueli Zhu Xingqiang Pan Jie Sun Xiang Gao Yi Huang Yi Huang Yi Huang DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males Frontiers in Aging Neuroscience PNPLA6 DNA methylation mRNA expression age intracranial aneurysms |
| title | DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males |
| title_full | DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males |
| title_fullStr | DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males |
| title_full_unstemmed | DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males |
| title_short | DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males |
| title_sort | dna methylation of patatin like phospholipase domain containing protein 6 gene contributes to the risk of intracranial aneurysm in males |
| topic | PNPLA6 DNA methylation mRNA expression age intracranial aneurysms |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.885680/full |
| work_keys_str_mv | AT shengjunzhou dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT shengjunzhou dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT junjunzhang dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT chenhuizhou dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT chenhuizhou dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT fanyonggong dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT xuelizhu dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT xingqiangpan dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT jiesun dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT xianggao dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT yihuang dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT yihuang dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales AT yihuang dnamethylationofpatatinlikephospholipasedomaincontainingprotein6genecontributestotheriskofintracranialaneurysminmales |