Cargando…
Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms
DNA methylation at the gene promoter region is reportedly involved in the development of intracranial aneurysm (IA). This study aims to investigate the methylation levels of polypyrimidine tract-binding protein 1 (PTBP1) in IA, as well as its potential to predict IA. Forty-eight patients with IA and...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292010/ https://www.ncbi.nlm.nih.gov/pubmed/34295240 http://dx.doi.org/10.3389/fnagi.2021.688179 |
_version_ | 1783724759768367104 |
---|---|
author | Wang, Zhepei Zhou, Shengjun Zhao, Jikuang Nie, Sheng Sun, Jie Gao, Xiang Lenahan, Cameron Lin, Zhiqin Huang, Yi Chen, Gao |
author_facet | Wang, Zhepei Zhou, Shengjun Zhao, Jikuang Nie, Sheng Sun, Jie Gao, Xiang Lenahan, Cameron Lin, Zhiqin Huang, Yi Chen, Gao |
author_sort | Wang, Zhepei |
collection | PubMed |
description | DNA methylation at the gene promoter region is reportedly involved in the development of intracranial aneurysm (IA). This study aims to investigate the methylation levels of polypyrimidine tract-binding protein 1 (PTBP1) in IA, as well as its potential to predict IA. Forty-eight patients with IA and 48 age- and sex-matched healthy controls were recruited into this study. Methylation levels of CpG sites were determined via bisulfite pyrosequencing. The PTBP1 levels in the blood were determined using a real-time quantitative reverse transcription-polymerase chain reaction test. Significant differences were found between IAs and controls in CpG1 (p = 0.001), CpG2 (p < 0.001), CpG3 (p = 0.037), CpG4 (p = 0.003), CpG5 (p = 0.006), CpG6 (p = 0.02), and mean methylation (p < 0.001). The mRNA level of PTBP1 in the blood was much lower in IAs compared with controls (p = 0.002), and the PTBP1 expression was significantly associated with DNA methylation promoter levels in individuals (r = −0.73, p < 0.0001). In addition, stratification analysis comparing smokers and non-smokers revealed that tobacco smokers had significantly higher levels of DNA methylation in PTBP1 than non-smokers (p = 0.002). However, no statistical difference in PTBP1 methylation was found between ruptured and unruptured IA groups (p > 0.05). The ROC analyses of curves revealed that PTBP1 methylation may be a predictor of IA regardless of sex (both sexes, area under curve (AUC) = 0.78, p < 0.0001; male, AUC = 0.76, p = 0.002; female, AUC = 0.79, p < 0.0001). These findings suggest that long-term tobacco smoke exposure led to DNA methylation in the promoter region of the PTBP1 gene, which further decreased PTBP1 gene expression and participated in the pathogenesis of IA. The methylation of PTBP1 may be a potential predictive marker for the occurrence of IA. |
format | Online Article Text |
id | pubmed-8292010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82920102021-07-21 Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms Wang, Zhepei Zhou, Shengjun Zhao, Jikuang Nie, Sheng Sun, Jie Gao, Xiang Lenahan, Cameron Lin, Zhiqin Huang, Yi Chen, Gao Front Aging Neurosci Neuroscience DNA methylation at the gene promoter region is reportedly involved in the development of intracranial aneurysm (IA). This study aims to investigate the methylation levels of polypyrimidine tract-binding protein 1 (PTBP1) in IA, as well as its potential to predict IA. Forty-eight patients with IA and 48 age- and sex-matched healthy controls were recruited into this study. Methylation levels of CpG sites were determined via bisulfite pyrosequencing. The PTBP1 levels in the blood were determined using a real-time quantitative reverse transcription-polymerase chain reaction test. Significant differences were found between IAs and controls in CpG1 (p = 0.001), CpG2 (p < 0.001), CpG3 (p = 0.037), CpG4 (p = 0.003), CpG5 (p = 0.006), CpG6 (p = 0.02), and mean methylation (p < 0.001). The mRNA level of PTBP1 in the blood was much lower in IAs compared with controls (p = 0.002), and the PTBP1 expression was significantly associated with DNA methylation promoter levels in individuals (r = −0.73, p < 0.0001). In addition, stratification analysis comparing smokers and non-smokers revealed that tobacco smokers had significantly higher levels of DNA methylation in PTBP1 than non-smokers (p = 0.002). However, no statistical difference in PTBP1 methylation was found between ruptured and unruptured IA groups (p > 0.05). The ROC analyses of curves revealed that PTBP1 methylation may be a predictor of IA regardless of sex (both sexes, area under curve (AUC) = 0.78, p < 0.0001; male, AUC = 0.76, p = 0.002; female, AUC = 0.79, p < 0.0001). These findings suggest that long-term tobacco smoke exposure led to DNA methylation in the promoter region of the PTBP1 gene, which further decreased PTBP1 gene expression and participated in the pathogenesis of IA. The methylation of PTBP1 may be a potential predictive marker for the occurrence of IA. Frontiers Media S.A. 2021-07-06 /pmc/articles/PMC8292010/ /pubmed/34295240 http://dx.doi.org/10.3389/fnagi.2021.688179 Text en Copyright © 2021 Wang, Zhou, Zhao, Nie, Sun, Gao, Lenahan, Lin, Huang and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Wang, Zhepei Zhou, Shengjun Zhao, Jikuang Nie, Sheng Sun, Jie Gao, Xiang Lenahan, Cameron Lin, Zhiqin Huang, Yi Chen, Gao Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms |
title | Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms |
title_full | Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms |
title_fullStr | Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms |
title_full_unstemmed | Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms |
title_short | Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms |
title_sort | tobacco smoking increases methylation of polypyrimidine tract binding protein 1 promoter in intracranial aneurysms |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292010/ https://www.ncbi.nlm.nih.gov/pubmed/34295240 http://dx.doi.org/10.3389/fnagi.2021.688179 |
work_keys_str_mv | AT wangzhepei tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms AT zhoushengjun tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms AT zhaojikuang tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms AT niesheng tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms AT sunjie tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms AT gaoxiang tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms AT lenahancameron tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms AT linzhiqin tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms AT huangyi tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms AT chengao tobaccosmokingincreasesmethylationofpolypyrimidinetractbindingprotein1promoterinintracranialaneurysms |